BACKGROUND: High on-treatment platelet reactivity (HTPR) has been suggested as a risk factor for patients with ischemic vascular disease. We explored a predictive model of platelet reactivity to clopidogrel and the relationship with clinical outcomes. METHODS: A total of 441 patients were included. Platelet reactivity was measured by light transmittance aggregometry after receiving dual antiplatelet therapy. HTPR was defined by the consensus cutoff of maximal platelet aggregation >46% by light transmittance aggregometry. CYP2C19 loss-of-function polymorphisms were identified by DNA microarray analysis. The data were compared by binary logistic regression to find the risk factors. The primary endpoint was major adverse clinical events (MACEs), and patients were followed for a median time of 29 months. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the patients with HTPR and non-HTPR. RESULTS: The rate of HTPR was 17.2%. Logistic regression identified the following predictors of HTPR: age, therapy regimen, body mass index, diabetes history, CYP2C192, or CYP2C193 variant. The area under the curve of receiver operating characteristic for the HTPR predictive model was 0.793 (95% confidence interval: 0.738-0.848). Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE than those with non-HTPR (21.1% vs. 9.9%; χ = 7.572, P = 0.010). CONCLUSIONS Our results suggest that advanced age, higher body mass index, treatment with regular dual antiplatelet therapy, diabetes, and CYP2C192 or CYP2C193 carriers are significantly associated with HTPR to clopidogrel. The predictive model of HTPR has useful discrimination and good calibration and may predict long-term MACE.
Aged ; Blood Platelets ; drug effects ; Clopidogrel ; pharmacology ; therapeutic use ; Coronary Artery Disease ; metabolism ; prevention & control ; Cytochrome P-450 CYP2C19 ; metabolism ; Female ; Genotype ; Glycated Hemoglobin A ; metabolism ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Ischemia ; metabolism ; prevention & control ; Regression Analysis

BACKGROUND: Previous studies have reported that fasting insulin and blood glucose levels are higher in postmenopausal than in premenopausal women and that insulin resistance was more serious in postmenopausal women. The effects of menopause on glucose metabolism have been well studied, but it is unclear whether age at menopause onset is associated with fasting blood sugar and HbA1c levels. The purpose of this study is to determine the effect of menopause age on diabetes and prediabetes.METHODS: We retrospectively analyzed data from the Sixth Korea National Health and Nutrition Examination Survey (2013–2015). The participants were 2,156 naturally menopausal women, except diabetes, stroke, coronary artery disease and cancer patients. The study population was divided into four groups according to the age of natural menopause onset ( < 40, 40–44, 45–55, and ≥56 years). Diagnosis of diabetes and prediabetes was based on the American Diabetes Association guideline. The association between menopause age and diabetes or prediabetes was analyzed by multiple logistic regression.RESULTS: Women reaching menopause at 40–44 years were 4.901 times more likely to have diabetes (odds ratio [OR], 4.901; 95% confidence interval [95% CI], 1.353–17.756, P=0.016) than those who reached menopause at an age of ≥56 years. Women with menopause at age < 40 years were 2.839 times more likely to have diabetes or prediabetes (OR, 2.839; 95% CI, 1.012–7.968, P=0.047).CONCLUSION: Women with premature menopause (< 40 years) have high risk of developing diabetes or prediabetes, and women with a menopause age of 40–44 years have high risk of developing diabetes.
Blood Glucose ; Coronary Artery Disease ; Diabetes Mellitus ; Diagnosis ; Fasting ; Female ; Glucose ; Humans ; Insulin ; Insulin Resistance ; Korea ; Logistic Models ; Menopause ; Menopause, Premature ; Metabolism ; Nutrition Surveys ; Prediabetic State ; Retrospective Studies ; Stroke

OBJECTIVETo study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL).

METHODSA total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC).

RESULTSThe serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05).

CONCLUSIONSIL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

Acute Disease ; Atrial Natriuretic Factor ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Cholesterol ; blood ; Coronary Artery Disease ; blood ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Interleukin-1beta ; blood ; Interleukins ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Procalcitonin ; blood ; Protein Precursors ; blood ; Triglycerides ; blood

BackgroundIt is known that there is a definite association between platelet distribution width (PDW) and poor prognosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, there are no data available regarding the prognostic significance of PDW for in-stent restenosis (ISR) in patients with CAD and T2DM. We aimed to determine the value of PDW on admission that predicted ISR in patients with CAD and T2DM.

MethodsBetween January 2012 and December 2013, a total of 5232 consecutive patients diagnosed with CAD and T2DM undergoing percutaneous coronary intervention were admitted. Three years of retrospective follow-up was undertaken. A total of 438 patients with second angiography operations were included. ISR was defined as ≥50% luminal stenosis of the stent or peri-stent segments. Continuous data were presented as the mean ± standard deviation or median (P, P) and were compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical variables were presented as percentages and were compared by Chi-square test or Fisher's exact test. The association between PDW and ISR was calculated by logistic regression analysis. A two-sided value of P < 0.05 was considered statistically significant. Statistical analyses were performed by SPSS version 22.0 for windows.

ResultsFifty-nine patients with ISR, accounting for 13.5% of the total, were included. ISR was significantly more frequent in patients with higher PDW quartiles compared with lower quartiles. We observed that PDW had a strong relationship with mean platelet volume (r = 0.647, 95% confidence interval [CI]: 0.535-0.750, P < 0.0001). The receiver-operating characteristic curves showed that the PDW cutoff value for predicting ISR rate was 13.65 fl with sensitivity of 59.3% and specificity of 72.4% (area under curve [AUC] = 0.701, 95% CI: 0.625-0.777, P < 0.001). Multivariate analysis showed that the risk of ISR increased approximately 30% when PDW increased one unit (odds ratio [OR]: 1.289, 95% CI: 1.110-1.498, P = 0.001). Patients with higher PDW, defined as more than 13.65 fl, had a 4-fold higher risk of ISR compared with lower PDW (OR: 4.241, 95% CI: 1.879-9.572, P = 0.001). Furthermore, when patients were divided by PDW quartiles values, PDW was able to predict ISR (Q2: OR = 0.762, 95% CI: 0.189-3.062, P = 0.762; Q3: OR = 2.782, 95% CI: 0.865-8.954, P = 0.086; and Q4: OR = 3.849, 95% CI: 1.225-12.097, P = 0.021, respectively; P for trend <0.0001).

ConclusionPDW is an independent predictor of ISR in patients with CAD and T2DM.

Adult ; Aged ; Blood Platelets ; metabolism ; Coronary Artery Disease ; metabolism ; therapy ; Coronary Restenosis ; metabolism ; therapy ; Diabetes Mellitus, Type 2 ; metabolism ; therapy ; Female ; Humans ; Male ; Mean Platelet Volume ; Middle Aged ; Percutaneous Coronary Intervention ; Retrospective Studies

BACKGROUNDThe clinical significance of metabolic syndrome (MS) score, MS, and its individual components with respect to risk prediction of coronary artery disease (CAD) remains unclear. The objective of this study was to investigate whether and to what extent MS score, MS, and its individual components were related to the risk of CAD.

METHODSAmong 1191 participants who underwent coronary angiography for the confirmation of suspected myocardial ischemia, 858 were included in this study according to the inclusion criteria from September 2010 to June 2013. MS was diagnosed with the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria. The severity of coronary atherosclerosis was assessed by Gensini score.

RESULTSThe results showed that the age- and sex-adjusted odds ratios (OR s) for CAD were as follows: MS score, 1.327; MS, 2.013; elevated waist circumference, 1.447; reduced high-density lipoprotein cholesterol, 1.654; and elevated fasting glucose, 1.782; all P < 0.05; whereas for elevated triglycerides, 1.324, and elevated blood pressure, 1.342, both P > 0.05. After multivariate adjustment, results showed that only MS and elevated fasting glucose were significantly associated with CAD (OR, 1.628, 95% confidence interval [CI], 1.151-2.305, P = 0.006 for elevated fasting glucose, and OR, 1.631, 95% CI, 1.208-2.203, P = 0.001 for MS). The study showed that only MS score and elevated fasting glucose were significantly associated with Gensini score (standardized coefficient, 0.101, P = 0.031 for elevated fasting glucose and standardized coefficient, 0.103, P = 0.009 for MS score).

CONCLUSIONSThe present study demonstrated that MS score, MS, and its individual components might have different contributions to CAD prevalence and severity. MS and elevated fasting glucose were independent risk factors for the prevalence of angiographic CAD whereas MS score and elevated fasting glucose were significantly associated with the severity of CAD.

Adult ; Aged ; Aged, 80 and over ; Blood Glucose ; metabolism ; Blood Pressure ; physiology ; Coronary Angiography ; Coronary Artery Disease ; epidemiology ; metabolism ; pathology ; Fasting ; blood ; Female ; Humans ; Lipoproteins, HDL ; blood ; Male ; Metabolic Syndrome ; epidemiology ; metabolism ; pathology ; Middle Aged ; Prevalence ; Risk Factors ; Triglycerides ; blood

Vitamin D is a molecule that is actively involved in multiple metabolic pathways. It is mostly known for its implications related to calcium metabolism. It has also been determined that it actively participates in the cardiovascular system, influencing blood pressure, coronary artery disease and other vascular diseases, such as heart failure and atrial fibrillation. Furthermore, it has been established that this vitamin is extensively involved in the regulation of both the renin angiotensin aldosterone system and the immune system. In this review, we present the different vitamin D metabolic pathways associated with the cardiovascular pathophysiology, and we include studies in animal and human models, as well as some of the controversies found in the literature. This review also incorporates an overview of the implications in the molecular biology and public health fields.
Animals ; Atrial Fibrillation ; Blood Pressure ; Calcium ; Cardiovascular Diseases* ; Cardiovascular System ; Coronary Artery Disease ; Heart Failure ; Humans ; Immune System ; Metabolic Networks and Pathways ; Metabolism ; Molecular Biology ; Public Health ; Renin-Angiotensin System ; Vascular Diseases ; Vitamin D* ; Vitamins*

BACKGROUNDPercutaneous coronary intervention (PCI) causes endothelial damage, resulting in an inflammatory response with elevation of markers such as high-sensitive C-reactive protein (hs-CRP) and vascular cell adhesion molecule-1 (VCAM-1), which are associated with restenosis after PCI. Evidence suggests that microRNA-126 (miR-126) plays an important role in vascular inflammation, but its correlation with PCI-mediated inflammation has not been investigated. In this study, we investigated the effect of PCI on circulating miR-126 and inflammation markers such as hs-CRP and VCAM-1.

METHODSWe enrolled 130 patients with coronary artery disease (CAD) in the Second Hospital of Jilin University from October 2015 to December 2015. Among them, 82 patients with CAD, defined as at least one major epicardial vessel with >70% stenosis who planned to undergo PCI, were divided into acute coronary syndrome (ACS) group (46 patients) and stable angina (SA) group (36 patients). Forty-eight patients confirmed by coronary angiography without PCI were used as controls. The plasmas of all patients were collected prior to PCI and at 30 min, 24 h, and 72 h after PCI. The plasma VCAM-1 and hs-CRP were detected by enzyme-linked immunosorbent assay, and the miR-126 was evaluated by quantitative reverse transcription-polymerase chain reaction.

RESULTSPlasma concentrations of hs-CRP and VCAM-1 in patients with either ACS (n = 46) or SA (n = 36) were significantly higher than in controls (n = 48) (P < 0.01) prior to PCI, and increased further at 24 h and 72 h after PCI, compared with prior PCI. Moreover, VCAM-1 was positively correlated with balloon time and pressure. In contrast, the plasma concentration of miR-126 was significantly lower in patients with CAD than in controls, and further decreased with time post-PCI. A negative correlation was observed between miR-126 and hs-CRP and VCAM-1 at 72 h after PCI.

CONCLUSIONThere was a negative correlation of miR-126 with the PCI-induced markers of inflammation such as hs-CRP and VCAM-1.

Acute Coronary Syndrome ; blood ; Angina, Stable ; blood ; C-Reactive Protein ; metabolism ; Coronary Angiography ; Coronary Artery Disease ; blood ; surgery ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; MicroRNAs ; blood ; Middle Aged ; Percutaneous Coronary Intervention ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Cell Adhesion Molecule-1 ; blood

BACKGROUND: To determine the associations between serum osteocalcin level and insulin resistance, coronary atherosclerosis by using dual-source coronary computed tomography angiography. METHODS: A total of 98 subjects (24 men and 74 women) were selected for this retrospective cross-sectional study who voluntarily visited a health examination center for routine health check-up including the blood test for serum osteocalcin level and coronary computed tomography angiography. Multiple regression analysis was used to determine which variables were independently related to osteocalcin levels and coronary atherosclerosis. RESULTS: Stepwise multiple regression analysis adjusted for age, sex, menopausal status, body mass index, serum alkaline phosphatase, serum calcium and phosphate showed that osteocalcin negatively correlated with serum glucose (β=-0.145, P=0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) index (β=-1.794, P=0.027) independently. The age, serum glucose, smoking status but not osteocalcin level were independent risk factors for coronary atherosclerosis by use of multiple logistic regression analysis after controlling for other variables. CONCLUSIONS: Serum osteocalcin level was inversely associated with fasting glucose level and insulin resistance measured by HOMA-IR, suggesting that osteocalcin is important for glucose metabolism. However, in this study, no significant difference was observed in the serum osteocalcin level according to the presence of coronary atherosclerotic plaques.
Alkaline Phosphatase ; Angiography ; Blood Glucose ; Body Mass Index ; Calcium ; Coronary Angiography ; Coronary Artery Disease* ; Cross-Sectional Studies ; Fasting ; Glucose ; Hematologic Tests ; Homeostasis ; Humans ; Insulin Resistance* ; Insulin* ; Logistic Models ; Male ; Metabolism ; Osteocalcin* ; Plaque, Atherosclerotic ; Retrospective Studies ; Risk Factors ; Smoke ; Smoking

BACKGROUNDWe investigated whether and to what extent the ratio between circulating fibrinogen (Fg) and its degradation products (FDP) reflects the severity of coronary artery disease (CAD) in type 2 diabetic patients.

METHODSPlasma levels of Fg and FDP were determined, and Fg/FDP ratio was calculated in 344 consecutive patients with type 2 diabetes and chest pain on exertion undergoing coronary angiography. The severity of CAD was evaluated by the number of significant CAD (>50% luminal diameter narrowing) and Gensini score.

RESULTSPlasma Fg was higher, but Fg/FDP ratio was lower in patients with significant CAD (n = 255) compared with those without (n = 89), due to a disproportionate increase in FDP. Fg and FDP correlated positively, while Fg/FDP ratio negatively, with the number of diseased coronary arteries and the tertile of Gensini score (all P values for trend < 0.01). After adjusting for age, sex, risk factors for CAD, lipid profiles, glycosylated hemoglobin A1c, creatinine, leukocyte count, and high-sensitivity C-reactive protein, Fg/FDP ratio remained an independent determinant for multivessel coronary disease (MVD) (odds ratio [OR], 0.869; 95% confidence interval [CI], 0.788-0.958, P = 0.005) and high tertile of Gensini score (OR, 0.797, 95% CI, 0.682-0.930, P = 0.004). The area under the curve of Fg/FDP ratio was larger than that of Fg for predicting the presence of MVD (0.647 vs. 0.563, P = 0.048) and Gensini score ≥ 30 (0.656 vs. 0.538, P = 0.026).

CONCLUSIONSElevated plasma Fg and FDP level and reduced Fg/FDP ratio are associated with presence of CAD, and Fg/FDP ratio is superior to Fg in reflecting severe coronary atherosclerosis for patients with type 2 diabetes.

Aged ; Coronary Angiography ; Coronary Artery Disease ; blood ; diagnosis ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; Female ; Fibrin ; metabolism ; Fibrinogen ; metabolism ; Humans ; Male ; Middle Aged

BACKGROUND/AIMS: The aim was to determine which of three sets of metabolic syndrome (MetS) criteria (International Diabetes Federation [IDF], National Cholesterol Education Program Adult Treatment Panel III [ATP III], and European Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary artery calcification (CAC) score in a cross-sectional study. This has not been evaluated in previous studies. METHODS: A total of 24,060 subjects were screened for CAC by multi-detector computed tomography. The presence of CAC was defined as a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three different sets of MetS criteria and according to number of MetS components. RESULTS: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS, as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%, 25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for multivariate regression models revealed no significant difference among the three sets of criteria. After adjustment for risk factors, the ATP III criteria produced a slightly higher odds ratio for CAC compared with the other criteria, but this difference was not significant. The risk factor-adjusted odds ratio for the presence of CAC increased from 1 to 1.679 as the number of MetS components defined by ATP III increased from 0 to > or = 3 (p for trend < 0.001). CONCLUSIONS: The presence of MetS was associated with the presence of CAC. There was no significant difference among the three sets of MetS criteria in terms of the ability to predict CAC. An increase in the number of MetS components was associated with an increased odds of CAC.
Adult ; Asymptomatic Diseases ; Biological Markers/blood ; Calcium/*analysis ; Coronary Angiography/methods ; Coronary Artery Disease/blood/*epidemiology/radiography ; Coronary Vessels/*chemistry/radiography ; Cross-Sectional Studies ; Female ; Humans ; Male ; Metabolic Syndrome X/blood/diagnosis/*epidemiology ; Middle Aged ; Multidetector Computed Tomography ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Prevalence ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors ; Vascular Calcification/blood/*epidemiology/metabolism/radiography