Prostaglandin E2-Transporting Pathway and Its Roles via EP2/EP4 in Cultured Human Dental Pulp.

INTRODUCTION: Prostaglandin E2 (PGE2) exerts biological actions through its transport pathway involving intracellular synthesis, extracellular transport, and receptor binding. This study aimed to determine the localization of the components of the PGE2-transporting pathway in human dental pulp and explore the relevance of PGE2 receptors (EP2/EP4) to angiogenesis and dentinogenesis. METHODS: Protein localization of microsomal PGE2 (mPGES)synthase, PGE2 transporters (multidrug resistance-associated protein-4 [MRP4] and prostaglandin transporter [PGT]), and EP2/EP4 was analyzed using double immunofluorescence staining. Tooth slices from human third molars were cultured with or without butaprost (EP2 agonist) or rivenprost (EP4 agonist) for 1 week. Morphometric analysis of endothelial cell filopodia was performed to evaluate angiogenesis, and real-time polymerase chain reaction was performed to evaluate angiogenesis and odontoblast differentiation markers. RESULTS: MRP4 and PGT were colocalized with mPGES and EP2/EP4 in odontoblasts and endothelial cells. Furthermore, MRP4 was colocalized with mPGES and EP4 in human leukocyte antigen-DR-expressing dendritic cells. In the tooth slice culture, EP2/EP4 agonists induced significant increases in the number and length of filopodia and mRNA expression of angiogenesis markers (vascular endothelial growth factor and fibroblast growth factor-2) and odontoblast differentiation markers (dentin sialophosphoprotein and collagen type 1). CONCLUSIONS: PGE2-producing enzyme (mPGES), transporters (MRP4 and PGT), and PGE2-specific receptors (EP2/EP4) were immunolocalized in various cellular components of the human dental pulp. EP2/EP4 agonists promoted endothelial cell filopodia generation and upregulated angiogenesis- and odontoblast differentiation-related genes, suggesting that PGE2 binding to EP2/EP4 is associated with angiogenic and dentinogenic responses.

Melanotic neuroectodermal tumor of infancy in the mandible: A case report.

RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

Understanding of antidiabetic medication is associated with blood glucose in patients with type 2 diabetes: At baseline date of the KAMOGAWA-DM cohort study.

AIMS/INTRODUCTION: Medication adherence, which is decreased by a poor understanding of medications, has a close association with blood glucose level in patients with type 2 diabetes. However, a relationship between the understanding of antidiabetic medication and blood glucose level in patients with type 2 diabetes is unclear. Here, we aimed to investigate the relationship between the understanding of antidiabetic medication and blood glucose level in patients with type 2 diabetes. MATERIALS AND METHODS: Lifestyle factors were evaluated by a questionnaire method, in the present cross-sectional study. Poor understanding of antidiabetic medication (PUAD) was defined as a discrepancy between the answer and the actual use of oral antidiabetic medication on the questionnaire. Poor blood glucose level was defined as hemoglobin A1c ≥8%. To investigate the impact of PUAD on poor blood glucose level, propensity-score matching analysis was used to remove the bias of confounding variables, including sex, age, log (duration of diabetes +1), body mass index, number of oral antidiabetic medications, smoking status, alcohol drinking, exercise, nephropathy, neuropathy, oral antidiabetic medications and insulin. RESULTS: Among 479 patients, 40 patients (8.4%) were categorized into the PUAD group. The hemoglobin A1c of patients with PUAD was higher than that of patients without (7.5 [1.3] vs 7.2 [0.9]%, P = 0.041). In the propensity-matched 74 patients, PUAD was associated with poor blood glucose level (odds ratio 5.45, 95% confidence interval 1.54-25.8, P = 0.007) by logistic regression analysis. CONCLUSION: A poor understanding of antidiabetic medication is associated with poor blood glucose level in patients with type 2 diabetes.

Successful Endovascular Treatment for Aortic Thrombosis Due to Primary Antiphospholipid Syndrome: A Case Report and Literature Review.

A 60-year-old man with a history of Raynaud's phenomenon presented with bilateral intermittent claudication and an ulcer on his right toe. The ankle-brachial index of the right and left legs was 0.77 and 0.75, respectively. Laboratory data showed prolongation of the activated partial thromboplastin time and a positive result on the lupus anticoagulant test. Computed tomography angiography revealed isolated infrarenal aortic stenosis with irregular surface and noncalcified plaques. Intravascular ultrasonography examination demonstrated a noncalcified, irregular, and mobile plaque, suggestive of abdominal aortic thrombosis. In addition to anticoagulant and dual antiplatelet therapy, endovascular treatment was performed. A total of three 40-mm-long balloon-expandable stents were successfully implanted on a 15-mm balloon. The final angiography showed good results except for minimal plaque shifting in the terminal aorta. Three months later, the ulcer resolved and a final diagnosis of primary antiphospholipid syndrome (APS) was made. Clinicians should recognize that APS can affect the abdominal aorta, leading to aortic thrombosis. Endovascular treatment may be the one good treatment option for this rare condition.

Two-Wire Technique With a Gooseneck Snare to Bail Out the Tip Separation of a Crosser Catheter.

Tip separation of a Crosser catheter is a serious complication; however, there is limited information on bailout methods. Here, we describe a case of successful retrieval of the separated tip of a Crosser catheter using a 2-wire technique with a gooseneck snare. A 76-year-old woman with a history of hemodialysis and diabetes mellitus who developed ulcers on her right toes was diagnosed as having critical limb ischemia and underwent transfemoral antegrade endovascular treatment of the anterior tibial artery (ATA). A 0.014-inch guidewire was passed through the ATA chronic total occlusion, and then a Crosser catheter was advanced along the wire. During catheter withdrawal, the tip completely detached from the shaft and remained in the ATA. We passed another 0.014-inch guidewire into the distal ATA through the small space beside the tip. A gooseneck snare catheter was advanced to the distal side of the tip along the new wire, and subsequently the 2 wires were entrapped by the snare. The detached tip was finally retrieved with the entire system as a unit and successfully withdrawn into the guiding sheath with no complications. Interventionists should be familiar with the bailout method of this unfavorable complication. Our technique may be widely adapted for various situations involving this complication.

Late-night-dinner is associated with poor glycemic control in people with type 2 diabetes: The KAMOGAWA-DM cohort study.

Skipping breakfast or irregular breakfast is associated with poor glycemic control. However, a relationship between the timing of dinner and glycemic control in people with type 2 diabetes remains indefinite. Therefore, we investigated the relationship between late-night-dinner and glycemic control in people with type 2 diabetes. We performed questionnaire survey for lifestyle factors in this cross-sectional study. We defined having dinner later than eight pm as late-night-dinner. We examined the differences in clinical and metabolic parameters between those who have late-night-dinner and those who do not have. We also examined the relationship between late-night-dinner and HbA1c, using multiple regression analysis. Ninety-five people (23.2%) had a late-night-dinner, among 409 people with type 2 diabetes. Metabolic parameters (mean (SD) or median (interquartile range)) of people with late-night-dinner were worse than those of without, including body mass index (BMI) (24.4 (4.0) vs. 23.2 (3.4) kg/m2, p = 0.006), triglycerides (1.5 (1.1-2.1) vs. 1.2 (0.8-1.7) mmol/L, p < 0.001), HDL-cholesterol (1.4 (0.4) vs. 1.6 (0.4) mmol/L, p = 0.004) and hemoglobin A1c (58.1 (13.3) vs. 55.2 (10.2) mmol/mol, (7.5 (1.2) vs. 7.2 (0.9) %), p = 0.023)). Late-night-dinner (standardized regression coefficient = 0.13, p = 0.028) was associated with hemoglobin A1c after adjusting for age, BMI, sex, duration of diabetes, smoking, exercise, alcohol, snacking after dinner, nighttime sleep duration, time from dinner to bedtime, skipping breakfast, and medication for diabetes. Late-night-dinner is independently associated with poor glycemic control in people with type 2 diabetes.

A simple technique for repositioning of the mandible by a surgical guide prepared using a three-dimensional model after segmental mandibulectomy.

BACKGROUND: Mandibular reconstruction is performed after segmental mandibulectomy, and precise repositioning of the condylar head in the temporomandibular fossa is essential for maintaining preoperative occlusion. METHODS: In cases without involvement of soft tissue around the mandibular bone, the autopolymer resin in a soft state is pressed against the lower border of the mandible and buccal and lingual sides of the 3D model on the excised side. After hardening, it is shaved with a carbide bar to make the proximal and distal parts parallel to the resected surface in order to determine the direction of mandibular resection. On the other hand, in cases that require resection of soft tissue around the mandible such as cases of a malignant tumor, right and left mandibular rami of the 3D model are connected with the autopolymer resin to keep the preoperative position between proximal and distal segments before surgical simulation. The device is made to fit the lower border of the anterior mandible and the posterior border of the mandibular ramus. The device has a U-shaped handle so that adaptation of the device will not interfere with the soft tissue to be removed and has holes to be fixed on the mandible with screws. RESULTS: We successfully performed the planned accurate segmental mandibulectomy and the precise repositioning of the condylar head by the device. CONCLUSIONS: The present technique and device that we developed proved to be simple and useful for restoring the preoperative condylar head positioning in the temporomandibular fossa and the precise resection of the mandible.

Caffeine intake enhances the benefits of sodium glucose transporter 2 inhibitor.

BACKGROUND: The effect of sodium glucose transporter 2 (SGLT-2) inhibitors is dependent on the glomerular filtration rate. It has been reported that caffeine intake increases glomerular filtration rate. However, the effect of caffeine intake on urinary glucose excretion in patients who take SGLT-2 inhibitors is unclear. METHODS: Six patients with type 2 diabetes took part in a randomized, open-label, crossover pilot study. The patients took SGLT-2 inhibitors (ipragliflozin) for 9 days. On day 3, 6 and 9, the patients were assigned to one of three studies: Water 500, patients drank 500 mL of water in 3 h; Water 1500, patients drank 1500 mL of water in 3 h; and Caffeine 500, patients drank 500 mL of water with 400 mg of caffeine in 3 h. In all of the studies, the patients' urine was collected over a 6-h period. In addition, we enrolled 60 patients with type 2 diabetes who newly took SGLT-2 inhibitors in a 3-month follow-up cohort study to investigate the effect of caffeine intake on glucose control. Caffeine intake was evaluated using questionnaires. RESULTS: The 6-h median (interquartile range) urinary glucose excretion was 9.5 (8.5-9.7) g in Water 500, 12.2 (10.3-27.2) g in Water 1500 and 15.7 (11.4-21.4) g in Caffeine 500 (p = 0.005 vs Water 500). In the cohort study, multiple regression analysis demonstrated that log (caffeine intake) was associated with a change in HbA1c (ß = -0.299, p = 0.043) after adjusting for covariates. CONCLUSIONS: Caffeine intake enhanced the effect of SGLT-2 inhibitors. Copyright © 2016 John Wiley & Sons, Ltd.

Hemoglobin concentration and incident metabolic syndrome: a population-based large-scale cohort study.

Previous cross-sectional studies revealed an association between hemoglobin concentration and a prevalence of metabolic syndrome (MetS). However, the association between hemoglobin concentration and incident MetS remains to be elucidated. Thus, the aim of this study was to investigate the association between hemoglobin concentration and incident MetS. We enrolled 2695 subjects (1454 men and 1241 women) and performed 8-year follow-up cohort study. MetS was diagnosed, according to the joint interim statement, when a subject had three or more of the following components: hypertension; hyperglycemia; hypertriglyceridemia; low high-density lipoprotein cholesterol; and abdominal obesity. Logistic regression analyses were performed to assess the impact of hemoglobin concentration on incident MetS by adjusting for age, body mass index, lifestyle factors, including smoking status, habit of alcohol and habit of exercise, systolic blood pressure, fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol, creatinine, and uric acid. The highest (≥157 g/L) and third (151-156 g/L) hemoglobin concentration quartiles were associated with the increased risk of incident MetS compared to the lowest (<145 g/L) hemoglobin concentration quartile after adjusting for covariates in men (multivariate odds ratio (OR) 2.24, 95% CI 1.34-3.85, P = 0.0021 and multivariate OR 2.03, 95% CI 1.21-3.45, P = 0.0070). On the other hand, there was no association between hemoglobin concentration and incident MetS in women. Hemoglobin concentration was a novel risk marker for incident MetS in men.

Metabolically healthy obesity and risk of incident CKD.

BACKGROUND AND OBJECTIVES: Metabolically healthy obesity (MHO) is a unique obesity phenotype that apparently protects people from the metabolic complications of obesity. The association between MHO phenotype and incident CKD is unclear. Thus, this study investigated the association between MHO phenotype and incident CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 3136 Japanese participants were enrolled in an 8-year follow-up cohort study in 2001. Metabolically healthy status was assessed by common clinical markers: BP, triglycerides, HDL cholesterol, and fasting plasma glucose concentrations. Body mass index ≥25.0 kg/m(2) was defined as obesity. CKD was defined by proteinuria or eGFR of <60 ml/min per 1.73 m(2). To calculate the odds ratio for incident CKD, logistic regression analyses were performed. RESULTS: The crude incidence proportions of CKD were 2.6% (56 of 2122 participants) in participants with the metabolically healthy nonobesity phenotype, 2.6% (8 of 302) in those with the MHO phenotype, 6.7% (30 of 445) in those with the metabolically abnormal nonobesity phenotype, and 10.9% (29 of 267) in those with the metabolically abnormal obesity phenotype. Compared with metabolically healthy nonobesity phenotype, the odds ratios for incident CKD were 0.83 (95% confidence interval [95% CI], 0.36 to 1.72; P=0.64) for MHO, 1.44 (95% CI, 0.80 to 2.57; P=0.22) for metabolically abnormal nonobesity, and 2.80 (95% CI, 1.45 to 5.35; P=0.02) for metabolically abnormal obesity phenotype after adjustment for confounders, including age, sex, smoking statues, alcohol use, creatinine, uric acid, systolic BP, HDL cholesterol, and impaired fasting glucose or diabetes. CONCLUSION: MHO phenotype was not associated with higher risk of incident CKD.

Home blood pressure variability on one occasion is a novel factor associated with arterial stiffness in patients with type 2 diabetes.

Recent studies have suggested that not only mean blood pressure but also variability in blood pressure might be related to cardiovascular disease. The aim of this study was to investigate the association between home blood pressure variability on one occasion and markers of arterial stiffness in patients with type 2 diabetes. We investigated the relationship between the s.d. of clinic- or home-measured systolic blood pressure on one occasion and pulse wave velocity (PWV) in 332 patients with type 2 diabetes, and we evaluated whether the SD of clinic- or home-measured systolic blood pressure on one occasion was an independent determinant of PWV by multivariate linear regression analysis, after adjustment for known risk factors for arterial stiffness, including sex, age, duration of diabetes, body mass index, hemoglobin A1c, serum total cholesterol, triglycerides, smoking status, drinking alcohol, presence of antihypertensive medication, average systolic blood pressure and heart rate. Age, average morning home-measured systolic blood pressure, heart rate and PWV (r=0.259, P<0.0001) were positively correlated with the s.d. of morning home blood pressure on one occasion. Multiple regression analysis demonstrated that age, average morning home-measured systolic blood pressure (P=0.0019), heart rate and the s.d. of morning home-measured systolic blood pressure on one occasion (P=0.0159) were independently associated with PWV. In conclusion, home blood pressure variability on one occasion was correlated with PWV, independent of other known risk factors, in Japanese patients with type 2 diabetes.

Atrophic gastritis is associated with coronary artery disease.

Atrophic gastritis is characterized by chronic inflammation of gastric mucosa by Helicobacter pylori infection and other factors. Helicobacter pylori infection has been linked to coronary artery disease. To our knowledge, however, no reports are available on the relationship between atrophic gastritis and coronary artery disease. In this study, we investigated the relationship between atrophic gastritis, which is diagnosed based on serum pepsinogen levels (pepsinogen I ≤ 70 ng/mL and pepsinogen I/II ratio ≤ 3.0), and the prevalence of coronary artery disease in general Japanese population. Among 2,633 study subjects, 531 subjects (20.2%) were diagnosed as atrophic gastritis. The prevalence of coronary artery disease was higher in the atrophic gastritis-positive group than that in the atrophic gastritis-negative group (5.8% vs 2.8%, p = 0.0005). Multiple logistic regression analysis demonstrated that atrophic gastritis was independently associated with coronary artery disease (odds ratio, 1.67; 95% confidence interval, 1.03-2.72), after adjustment for age, sex, obesity, hypertension, diabetes mellitus, dyslipidemia, hyperuricemia, and habits of smoking and drinking. These results suggest that atrophic gastritis is an independent risk factor for coronary artery disease. Chronic inflammation of gastric mucosa may be associated with the prevalence of coronary artery disease.

Pepsinogen I/II ratio is related to glucose, triacylglycerol, and uric acid levels.

OBJECTIVE: Under- and overnutrition are associated with a worse prognosis and constitute independent risk factors for morbidity and mortality. It is increasingly important to understand the factors that affect nutritional and metabolic statuses. The purpose of this study was to assess the relation between the pepsinogen I/II ratio and several biochemical markers. METHODS: A cross-sectional study was performed in 1985 subjects who underwent a health screening test. Subjects had no medications for hyperuricemia, dyslipidemia, diabetes mellitus, or hypertension. All subjects were classified into two groups. Subjects with a pepsinogen I/II ratio below 3 were defined as having atrophic gastritis. The relations between the pepsinogen I/II ratio and several biochemical markers, including total cholesterol, triacylglycerol, uric acid, cholinesterase, and glucose levels, were evaluated. RESULTS: The presence of atrophic gastritis was significantly associated with age, smoking status, alcohol consumption, body mass index, and triacylglycerol, uric acid, cholinesterase, and hemoglobin levels. Multiple linear regression analysis demonstrated that the pepsinogen I/II ratio was an independent determinant of glucose level (ß = 0.104, P < 0.0001), triacylglycerol level (ß = 0.072, P = 0.0014), uric acid level (ß = 0.048, P = 0.0138), and hemoglobin (ß = 0.037, P = 0.0429) after adjustments for age, sex, smoking status, alcohol consumption, and body mass index. CONCLUSION: The pepsinogen I/II ratio was related to glucose, triacylglycerol, and uric acid levels. Such an association fosters the idea that a decreased pepsinogen I/II ratio seems favorable for the prevention of overnutrition.

Low urine pH Is a predictor of chronic kidney disease.

BACKGROUND/AIMS: A variety of risk factors for chronic kidney disease (CKD), including the metabolic syndrome, were recently reported. It has been suggested that a low urine pH is another characteristic of the metabolic syndrome. However, the relationship between urine pH and CKD remains to be elucidated. METHODS: A cohort study was performed on 1,811 subjects who underwent a health check-up, and we examined whether low urine pH could be a predictor of CKD. The following risk factors for CKD were evaluated: age, gender, history of alcohol intake and smoking, BMI, systolic blood pressure, fasting plasma glucose, total cholesterol, uric acid, total leukocyte count, CKD stage, fasting urine pH, and protein at baseline. RESULTS: We followed 1,811 subjects for a median period of 7.7 years. Three hundred and thirty-nine subjects developed stage 3 CKD defined as progression to estimated glomerular filtration rate < 60 ml/min/1.73 m(2). Multiple Cox regression analysis revealed that the adjusted HR (95% CI) for stage 3 CKD was 1.32 (1.06-1.65; p = 0.0129) in subjects with fasting urine pH 5.0-5.5 compared to subjects with pH 6.5-7.0. CONCLUSION: Our study suggests that low urine pH is an independent predictor of stage 3 CKD.

Eosinophil count is positively correlated with coronary artery calcification.

Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C-reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log(CAC+1), respectively. Positive correlations were found between log(CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log(CAC+1) and eGFR (r=-0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (ß=0.314, P<0.0001), sex (ß=0.124, P<0.0001), hypertension (ß=0.084, P=0.0008), DM (ß=0.108, P<0.0001), eGFR (ß=-0.079, P=0.0021) and eosinophil count (ß=0.147, P<0.0001) were independent determinants of log(CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD.

U-shaped relationship between insulin level and coronary artery calcification (CAC).

AIM: Recent studies have suggested that hyperinsulinemia is associated with high cardiovascular risk. The purpose of this study was to assess the relationship between the serum insulin level and coronary artery calcification (CAC). METHODS: We performed a cross-sectional study of 582 consecutive and nondiabetic participants with clinical suspicion of coronary heart disease, and assessed the CAC score determined by multislice computed tomography. A standard 75-g oral glucose tolerance test was performed and venous blood was collected at 0, 30, 60 and 120 min for the measurement of plasma glucose and serum insulin. Statistical analyses were conducted for 4 subgroups according to fasting insulin and insulin area under the concentration time curve (InsAUC). RESULTS: Mean log (CAC+1) and InsAUC were 1.6 and 109.1 µIU/mL, respectively. Unadjusted analysis demonstrated that the fasting insulin quartiles (p=0.0256) and InsAUC quartiles (p<0.0001) were significantly associated with log (CAC+1), and the lowest fasting insulin quartiles (p<0.0001) and the lowest InsAUC quartile (p=0.0006) had lower glucose AUC. Analysis of covariance demonstrated that the lowest InsAUC quartile had the highest log (CAC+1), and the highest InsAUC quartile had a higher log (CAC+1) than the second and third InsAUC quartiles, adjusted for several coronary risk factors (p<0.0001). CONCLUSION: The lowest InsAUC quartile was related to CAC, although the lowest InsAUC quartile maintained glucose homeostasis, in this study population. Not only hyperinsulinemia but also a low insulin level are independently associated with CAC.

Low serum bilirubin concentration is associated with coronary artery calcification (CAC).

BACKGROUND: Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis. The purpose of this study was to assess the correlation between serum bilirubin concentration and coronary artery calcification (CAC). METHODS: This study consisted of 637 participants and we evaluated the relationship between CAC score determined by multislice computed tomography and serum bilirubin concentration. RESULTS: An inverse correlation was found between serum bilirubin concentration and log(CAC+1) (r=-0.361, P<0.0001). Multiple regression analysis also demonstrated that age (beta=0.261, P=0.0125), systolic blood pressure (beta=0.153, P=0.0237), uric acid (beta=0.126, P=0.0441), estimated glomerular filtration rate (beta=-0.139, P=0.0416) and serum bilirubin concentration (beta=-0.281, P<0.0001) were independent determinants of log(CAC+1). An increment of 1 micromol/L in serum bilirubin concentration was associated with 14% decrease in the odds for CAC score > or =400 after adjustment for several risk factors. Both age and SBP were also positively associated with CAC score > or =400, but the odds ratio for CAC score > or =400 was greater for every 1 micromol/L increment in serum bilirubin concentration than for every 1-year increment in age and 1-mmHg increment in SBP. CONCLUSIONS: Low serum bilirubin concentration is associated with coronary artery calcification. Serum bilirubin concentration can be measured easily in the clinical laboratory and applied in medical practice, and low serum bilirubin concentration would be useful as a provisional new risk factor of CAC.