Impact of Chronic Kidney Disease on the Associations of Cardiovascular Biomarkers With Adverse Outcomes in Patients With Suspected or Known Coronary Artery Disease: The EXCEED-J Study.

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high-risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3-point MACE (3P-MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, cardiovascular death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt-1, NT-proBNP, and hs-cTnI, but not other biomarkers, were significantly associated with 3P-MACE, all-cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT-proBNP and hs-cTnI. NT-proBNP and hs-cTnI were also significantly associated with 5P-MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT-proBNP and hs-cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT-proBNP and hs-cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

Correction to: Non-autoimmune acute-onset type 1 diabetes mellitus newly developed in an elderly patient presenting elevation of serum pancreatic exocrine enzymes.

[This corrects the article DOI: 10.1007/s13340-021-00535-0.].

Non-autoimmune acute-onset type 1 diabetes mellitus newly developed in an elderly patient presenting elevation of serum pancreatic exocrine enzymes.

An 82 year-old female patient not suffering from diabetes was transported to our hospital with hyperglycemia (HbA1c 8.2%, blood glucose 584 mg/dL) and mildly increased levels of pancreatic exocrine enzymes (amylase 543 IU/L, lipase 59 U/L, elastase-1 479 ng/dL), while there were no findings indicating pancreatitis. Under a diagnosis of new-onset diabetes, she was discharged with oral hypoglycemic agents, as retention of insulin secretion function [blood glucose 117 mg/dL, serum connecting peptide immunoreactivity (CPR) 1.63 ng/mL] with normalization of the enzymes was confirmed following administration. However, at 73 days after the hospitalization, she returned with diabetic ketoacidosis (blood glucose 910 mg/dL, pH in blood gas analysis 7.15, total blood ketone bodies > 7000 µmol/L) with a transient repeated increase of the enzymes (amylase 382 IU/L, lipase 82 U/L, elastase-1 569 ng/dL) and without pancreatitis. Notably, depletion of insulin secretion (6.1 µg/day in urine, 0.36 ng/mL in serum CPR with no response in glucagon-loading test) was revealed, and serum CPR level remained low after discharge. Together with negative findings for islet-related autoantibodies, the patient was diagnosed with acute-onset type 1B diabetes (T1BD). In the present patient with acute-onset T1BD, a mild increase in pancreatic exocrine enzymes was repeatedly observed, which may mimic fulminant type and raise questions for us about the commonly accepted pathophysiology of T1D. These findings may help to clarify issues related to newly developed T1D in elderly individuals.

Soluble vascular endothelial growth factor receptor 2 and prognosis in patients with chronic heart failure.

AIMS: Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR-2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR-2 (sVEGFR-2) levels is associated with poor prognosis in patients with chronic heart failure (HF). METHODS AND RESULTS: We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR-2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all-cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR-2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (<40%). During the follow-up, 113 cardiovascular deaths, 211 all-cause deaths, 350 MACE, and 309 HF hospitalizations occurred. After adjustment for potential clinical confounders and established biomarkers [N-terminal B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein], a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death [hazard ratio (HR), 1.79; 95% confidence interval (CI), 1.16-2.74] and all-cause death (HR, 1.43; 95% CI, 1.04-1.94), but not with MACE (HR, 1.11; 95% CI, 0.86-1.43) or HF hospitalization (HR, 1.03; 95% CI, 0.78-1.35). The stratified analyses revealed that a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death (HR, 1.76; 95% CI, 1.07-2.85) and all-cause death (HR, 1.49; 95% CI, 1.03-2.15) in the high-NT-proBNP group (above the median), but not in the low-NT-proBNP group. Notably, the patients with high-NT-proBNP and low-sVEGFR-2 (below the 25th percentile) had a 2.96-fold higher risk (95% CI, 1.56-5.85) for cardiovascular death and a 2.40-fold higher risk (95% CI, 1.52-3.83) for all-cause death compared with those with low-NT-proBNP and high-sVEGFR-2. CONCLUSIONS: A low sVEGFR-2 value was independently associated with cardiovascular death and all-cause death in patients with chronic HF. These associations were pronounced in those with high NT-proBNP levels.

Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study.

Background Whether circulating growth differentiation factor 15 (GDF-15) levels differ according to smoking status and whether smoking modifies the relationship between GDF-15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF-15 and the impact of smoking status on the association between GDF-15 and all-cause death. GDF-15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF-15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log-transformed GDF-15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF-15. The prognostic value of GDF-15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Distinct Characteristics of VEGF-D and VEGF-C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background VEGF-D (vascular endothelial growth factor D) and VEGF-C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF-C level is inversely and independently associated with all-cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF-D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF-D was measured. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-I, and high-sensitivity C-reactive protein), and VEGF-C, the VEGF-D level was significantly associated with all-cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF-D, either alone or in combination with VEGF-C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all-cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF-D value seems to independently predict all-cause mortality.

Multicentre, open-label, randomised controlled clinical trial to assess the efficacy and safety of appropriate target values for lipid management in patients who have mild-to-moderate stenotic lesions with high-risk plaques in coronary arteries: study protocol.

INTRODUCTION: To detect patients at high risk of developing myocardial infarction, plaque characteristics as well as the degree of stenosis in coronary arteries should be evaluated. However, unstable plaque or severe calcification detected via coronary artery CT (CACT) is not reflected in risk stratification according to current guidelines. It is hypothesised that patients with high-risk findings on CACT (even those without proven history of coronary artery diseases; CAD) should be strictly managed to lower their low-density lipoprotein cholesterol (LDL-C) levels to targets of secondary prevention. Currently, however, there is no evidence based on prospective randomised intervention studies to prove this hypothesis. METHODS AND ANALYSIS: Patients with mild-to-moderate stenotic lesions with positive remodelling or severe calcification, but without any history of CAD, will be randomly allocated to group A (reduce LDL-C to <120~160 mg/dL according to the primary prevention criteria based on the Japan Atherosclerosis Society (JAS) Guideline for Prevention of Atherosclerotic Cardiovascular Diseases 2017) and group B (reduce LDL-C to <70 mg/dL according to the secondary prevention criteria for high risk based on the JAS Guideline). They will be strictly managed to achieve the LDL-C targets. We will follow-up and evaluate the composite endpoints consisting of major cardiovascular events (death from CAD, non-fatal myocardial infarction, operation for coronary revascularisation and stroke) and stenosis progression or new stenosis development for 3 years. ETHICS AND DISSEMINATION: The study was approved by the National Hospital Organization Central Research Ethics Committee. The results of this study are scheduled to be published within 2 years after study completion via conference presentation or journal publication. TRIAL REGISTRATION NUMBER: UMIN000031136.

VEGF-C and Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. However, the relationships of vascular endothelial growth factor-C ( VEGF -C), a central player in lymphangiogenesis, with mortality and cardiovascular events in patients with suspected or known coronary artery disease are unknown. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The primary predictor was serum levels of VEGF -C. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for established risk factors, VEGF -C levels were significantly and inversely associated with all-cause death (hazard ratio for 1- SD increase, 0.69; 95% confidence interval, 0.60-0.80) and cardiovascular death (hazard ratio, 0.67; 95% confidence interval, 0.53-0.87), but not with major adverse cardiovascular events (hazard ratio, 0.85; 95% confidence interval, 0.72-1.01). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF -C levels further improved the prediction of all-cause death, but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within 1717 patients with suspected coronary artery disease. Conclusions In patients with suspected or known coronary artery disease, a low VEGF -C value may independently predict all-cause mortality.

Hemodialysis membrane coated with a polymer having a hydrophilic blood-contacting layer can enhance diffusional performance.

PURPOSE: Currently, the foreign surfaces of various extracorporeal circulation devices are coated with a biocompatible polymer coating agent (BPA), which creates a hydrophilic blood-contacting layer to reduce thrombogenicity, while the membranes in hemodialyzers are not. We aimed to clarify other side effects of BPA-coated membranes by examining the diffusion performance in in vitro experiments. METHODS: We used a polyethersulfone membrane (sieving coefficient of albumin is ≤0.01) coated with BPA product, SEC-1TM (Toyobo), in a hemodialyzer. To estimate the diffusion rates of a wide range of molecules, 2 L of saline containing vancomycin, lysozyme, and albumin were recirculated in the circuit configured with a hemodialyzer, and dialyzed continuously using water. The concentrations of sodium, vancomycin, lysozyme, and albumin were measured every 5 minutes for 30 minutes and compared in experiments with BPA-coated (n = 4) and BPA-noncoated (n = 4) membranes. RESULTS: The removal rates of sodium and vancomycin after 5 minutes of dialysis (n = 24) were significantly higher in BPA-coated than noncoated membranes, while those of lysozyme and albumin were not significantly different. The removal rates of sodium and vancomycin after 30 minutes of dialysis (n = 4) were significantly higher, and those of lysozyme were significantly lower in BPA-coated than noncoated membranes, while those of albumin were not significantly different. CONCLUSIONS: The preliminary study suggests that BPA-coated membranes enhanced the diffusion rate of molecules with low and middle molecular weight without affecting the sieving coefficient of albumin. Thus, BPA coating can enhance the dialysis performance of membranes.

Primary cardiac rhabdomyosarcoma developed after receiving radiotherapy for left breast cancer 18 years prior.

The heart is an organ where primary malignant tumors rarely develop. In particular, the incidence of cardiac rhabdomyosarcoma (RMS) is extremely low. It has been reported that the risk of second malignant tumors in mediastinum is increased by radiotherapy in women with breast cancer. However, little is known about the association between irradiation to heart and cardiac RMS. Here, we report a case of a 68-year-old woman with primary cardiac RMS. She suddenly presented syncope at a workplace, and was taken to the emergency room at our hospital. Several imaging tests, including echocardiogram and cine magnetic resonance imaging, detected two tumors in the right ventricle (RV) and its outflow tract, which had almost obstructed the main trunk of the pulmonary artery (PA). To avoid sudden PA occlusion by the tumor, we emergently performed surgical excision of the tumors from the RV. Pathological analysis revealed that these tumors were embryonal type RMS. She had received radiotherapy after mastectomy for left breast cancer 18 years previously, and no recurrence of breast cancer had been detected. This cardiac RMS is considered as a second malignant tumor related to radiotherapy for breast cancer. .

Predictive value of serum dihomo-γ-linolenic acid level and estimated Δ-5 desaturase activity in patients with hepatic steatosis.

BACKGROUND: Hepatic steatosis is considered one of the features of metabolic syndrome (MetS). Polyunsaturated fatty acid (PUFA) metabolism is modulated in obesity. However, it has yet to be fully elucidated whether a serum PUFA profile is associated with hepatic steatosis. OBJECTIVE: We aimed to clarify the relationship between a serum PUFA profile and liver lipid content. METHODS: A cross-sectional study was conducted on 288 patients with dyslipidemia, diabetes, or coronary artery disease on statin therapy. Several PUFAs were measured, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) in serum lipids, and Δ-5 desaturase (D5D) activity was estimated by AA to DGLA ratio. Abdominal computed tomography (CT) measured visceral fat area (VFA) and the ratio of CT attenuation for liver to spleen (L/S). RESULTS: The L/S ratio showed significant correlations with serum DGLA level and D5D activity (p<0.0001 for both). Serum DGLA level and D5D activity were significantly correlated with body mass index (BMI) or VFA, and with Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) (p<0.0001 for all). Multivariate logistic analysis revealed that a high DGLA level or low D5D activity was a significant determinant for hepatic steatosis (p<0.0001 for both) independent of BMI and HOMA-IR. ROC analysis revealed that they significantly enhanced the value of MetS-related factors in predicting hepatic steatosis (p<0.05 for both). CONCLUSIONS: A high DGLA level and low D5D activity in serum lipids may be useful markers predicting hepatic steatosis incrementally to MetS-related conventional factors.

Prospects for clinical applications of polymer-coated haemoconcentrator on extracorporeal circuit in cardiopulmonary bypass surgeries.

PURPOSE: Extracorporeal circulation circuits used in cardiopulmonary bypass surgeries are increasingly being coated with polymer materials to reduce the thrombogenicity of extracorporeal devices. However, a haemoconcentrator, which corrects haematocrit and electrolyte imbalances, is not coated with polymers. In this study, we sought to assess the filtration performance of polymer-coated haemoconcentrators in order to obtain insight into their prospects for use in clinical applications. METHODS: In vitro experiments were performed to evaluate the water pressure and flow properties of polymer-coated haemoconcentrators by comparing 3 polymer-coated haemoconcentrators with 3 non-coated haemoconcentrators. The cross-sectional surfaces of both types of haemoconcentrators were observed using a scanning electron microscope (SEM). RESULTS: The slopes of the regression lines for estimating the filtrated fluid flow as a function of the transmembrane pressure were 6.286 ± 0.320 for polymer-coated haemoconcentrators and 3.712 ± 0.170 for non-coated haemoconcentrators. These slopes were found to be significantly different and indicate that the filtration velocity is enhanced in polymer-coated haemoconcentrators over that in non-coated haemoconcentrators. However, the hollow fibre damage observed by SEM was not shown to contribute to higher filtration flow in the polymer-coated haemoconcentrator. Taking these results into consideration, we hypothesise that a polymer coating makes a foreign surface on a hollow fibre slippery, owing to the hydrophobicity of the polymer, thereby enhancing the velocity of the filtration. CONCLUSIONS: The results of this preliminary investigation suggest that a polymer coating can enhance the filtration performance of a haemoconcentrator and that polymer-coated haemoconcentrators might be useful in clinical applications.

Is using an open-reservoir cardiopulmonary bypass circuit after 6 days on standby safe?

OBJECTIVES: To investigate the sterility and biocompatibility of a stored open-reservoir cardiopulmonary bypass circuit maintained on standby. METHODS: A total of four cardiopulmonary bypass circuits were assembled, primed and left to recirculate. One unit was placed in a positive-pressure operating room and the other three were placed in the intensive care unit. The primed solutions, which employed Ringer's acetate, hydroxyethylated starch and hydrate steroid, were sampled after 0, 24, 48, 72, 96, 120 and 144 h in all cardiopulmonary bypass circuits to measure the bacteria count, endotoxin count and chemical substances within the primed solution. Chemical substances were detected by assessing the following: the total organic carbon by the combustion oxidation infrared spectrometry, and molecular weight spread by gel permeation chromatography. The environments were left unattended and were uncovered during the storage period to mimic the clinical scenario. RESULTS: There were no bacteria in any of the primed solutions, and only very minute concentrations of endotoxins were detected, both in the operating room and in the intensive care unit. The total organic carbon concentration was slightly more concentrated in the 144-h samples when compared with that in the 0-h samples. However, the molecular weight spread of the 0-h sample was identical to that in the 144-h sample. DISCUSSION: With regard to the presence of bacteria and endotoxins, we noted that the hardshell reservoirs in the cardiopulmonary bypass circuit were effectively sealed and not invaded by bacteria. With regard to the presence of chemical substances, we noted that an increase in total organic carbon concentration was caused by bedewing, and that there was no release of chemical substances such as a polymer-coating agent, or other molecular materials in the primed solution. CONCLUSIONS: There was no contamination or release of chemical substances in 6-day old cardiopulmonary bypass circuits maintained on standby, confirming that they are safe to use in terms of sterility and biocompatibility.

Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk.

Obesity leads to the development of type 2 diabetes mellitus, which is a strong risk factor for cardiovascular disease. A better understanding of the molecular basis of obesity will lead to the establishment of effective prevention strategies for cardiovascular diseases. Adipocytes have been shown to generate a variety of endocrine factors termed adipokines/adipocytokines. Obesity-associated changes to these adipocytokines contribute to the development of cardiovascular diseases. Adiponectin, which is one of the most well-characterized adipocytokines, is produced exclusively by adipocytes and exerts insulin-sensitizing and anti-atherogenic effects. Obese subjects have lower levels of circulating adiponectin, and this is recognized as one of the factors involved in obesity-induced insulin resistance and atherosclerosis. Another pathophysiological feature of obesity may involve the low-grade chronic inflammation in adipose tissue. This inflammatory process increases oxidative stress in adipose tissue, which may affect remote organs, leading to the development of diabetes, hypertension, and atherosclerosis. Nuclear hormone receptors (NRs) regulate the transcription of the target genes in response to binding with their ligands, which include metabolic and nutritional substrates. Among the various NRs, peroxisome proliferator-activated receptor γ promotes the transcription of adiponectin and antioxidative enzymes, whereas mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid to induce oxidative stress in adipocytes. It is hypothesized that both play crucial roles in the pathophysiology of obesity-associated insulin resistance and cardiovascular diseases. Thus, reduced adiponectin and increased oxidative stress play pathological roles in obesity-associated insulin resistance to increase the cardiovascular disease risk, and various NRs may be involved in this pathogenesis.

Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases.

The recent increase in populations with obesity is a worldwide social problem, and the enhanced susceptibility of obese people to metabolic and cardiovascular diseases has become a growing health threat. An understanding of the molecular basis for obesity-associated disease development is required to prevent these diseases. Many studies have revealed that the mechanism involves various bioactive molecules that are released from adipose tissues and designated as adipocytokines/adipokines. Adiponectin is an adipocytokine that exerts insulin-sensitizing effects in the liver and skeletal muscle via adenosine monophosphate-activated protein kinase and proliferator-activated receptor α activation. Additionally, adiponectin can suppress atherosclerosis development in vascular walls via various anti-inflammatory effects. In contrast, oxidative stress is a harmful factor that systemically increases during obesity and promotes the development of diabetes, atherosclerosis, and various other diseases. In obese mice, oxidative stress is enhanced in adipose tissue before diabetes development, but not in the liver, skeletal muscle, and aorta, suggesting that in obesity, adipose tissue may be a major source of reactive oxygen species (ROS). ROS suppress adiponectin production in adipocytes. Treatment of obese mice with anti-oxidative agents improves insulin resistance and restores adiponectin production. Recent studies have demonstrated that adiponectin protects against oxidative stress-induced damage in the vascular endothelium and myocardium. Thus, decreased circulating adiponectin levels and increased oxidative stress, which are closely linked to each other, should be deeply involved in obesity-associated metabolic and cardiovascular disease pathogenesis.

Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and anti-diabetes medications on malondialdehyde-modified low-density lipoprotein levels in statin-treated diabetes patients with coronary artery disease.

BACKGROUND: A residual risk of cardiovascular disease tends to persist despite standard prevention therapy with statins. This may stem partly from increased oxidized low-density lipoprotein (LDL) levels. However, how oxidized LDL can be further reduced beyond statin therapy in high-risk diabetes patients remains unclear. We aimed to clarify the clinical factors associated with oxidized LDL levels in statin-treated high-risk diabetes patients. METHODS: This cross-sectional observational study included 210 diabetes patients with coronary artery diseases (CAD) who were treated with statins. We determined serum malondialdehyde-modified LDL (MDA-LDL), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), remnant lipoprotein cholesterol, hemoglobin (Hb) A1c, adiponectin, and C-reactive protein (CRP) levels and investigated the factors influencing the MDA-LDL level. RESULTS: In univariate analysis, the MDA-LDL level was significantly correlated with LDL cholesterol (p < 0.0001), TG (p < 0.0001), HDL cholesterol (p = 0.017), and adiponectin (p = 0.001) levels but not with age, body mass index, waist circumference, blood pressure, or HbA1c levels. Even after adjusting for the LDL cholesterol level, the correlations between the MDA-LDL level and the TG, HDL cholesterol, and adiponectin levels were still significant. Among these significant factors, multivariate analysis revealed that the MDA-LDL level was independently associated with the LDL cholesterol, TG, and HDL cholesterol but not with adiponectin levels. The MDA-LDL level was also significantly associated with the CRP level (p = 0.014) and the remnant lipoprotein cholesterol level (p < 0.0001) independently of the LDL cholesterol level. The number of metabolic syndrome (MS) components was significantly associated with the MDA-LDL/LDL cholesterol ratio (p < 0.0001). Furthermore, the use of metformin and α-glucosidase inhibitors was inversely associated with high MDA-LDL levels (p = 0.033 and 0.018, respectively). CONCLUSION: In statin-treated diabetes patients with CAD, the MDA-LDL level was significantly correlated with TG and HDL cholesterol levels. Adiponectin level was also significantly associated with the MDA-LDL level, but not independent of the above-mentioned factors. The management of dyslipidemic MS components, including the use of metformin or α-glucosidase inhibitors, may be important for reducing the oxidized LDL levels beyond statin therapy in high-risk diabetes patients.

Predictive value of adiponectin in patients with multivessel coronary atherosclerosis detected on computed tomography angiography.

AIM: Multislice computed tomography coronary angiography (CTCA) can be used to detect coronary plaques that predict the risk of cardiovascular events. This study aimed to identify the risk factors associated with the extent of coronary plaques detected using CTCA and to determine the value of adiponectin measurement for identifying high-risk patients with multivessel coronary atherosclerosis. METHODS: The study included 298 patients who underwent CTCA for coronary artery disease (CAD) screening between July 2008 and October 2011. We investigated the relationship between the extent of coronary atherosclerosis in terms of the number of diseased vessels and various risk factors, including the serum adiponectin level. RESULTS: The adiponectin level was found to be significantly associated with multivessel coronary atherosclerosis in a univariate analysis (p=0.001). A multivariate analysis revealed the adiponectin level to also be significantly associated with multivessel coronary atherosclerosis (p=0.01), independent of other significant risk factors, including an advanced age, male gender, diabetes mellitus (DM) and hypertension (HT). A receiver operating characteristic curve analysis revealed that a combination of these factors significantly predicted multivessel coronary atherosclerosis (area under the curve, 0.73;95% confidence interval, 0.67-0.78). As the number of these factors increased, the proportion of patients with multivessel coronary atherosclerosis increased, while the proportion of patients with normal coronary arteries decreased (p < 0.0001). CONCLUSIONS: A low adiponectin level combined with an advanced age, male gender, DM, and HT is independently and incrementally associated with multivessel coronary atherosclerosis. The number of factors may predict the extent of coronary atherosclerosis in patients without documented CAD.

A case of a young, healthy woman with spontaneous coronary artery dissection associated with oral contraceptive use: Long-term residual dissection of the coronary artery.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, typically affecting young, healthy women, particularly during the peripartum period. Oral contraceptive use is also recognized as a risk factor for SCAD. In the present report, we describe a case of a young woman with an anterior wall myocardial infarction caused by SCAD of the left anterior descending artery (LAD). The event was probably associated with the patient's oral contraceptive use. The patient underwent percutaneous coronary intervention, and she did not experience any recurrent chest pain or other cardiac symptoms. Although the coronary angiography revealed good LAD flow and no symptoms after 6 months, cardiac computed tomography and intravascular ultrasound revealed that LAD dissection was still present. We continued to closely follow-up the patient without initiating any additional intervention, and the patient has had no cardiac event for up to 4 years of follow-up. .

Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer.

Obesity, especially of the abdominal type, is a health problem that constitutes metabolic syndrome and increases the incidence of various diseases, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Various mechanisms linking obesity to these associated diseases have been postulated. One candidate is oxidative stress, which has been implicated in vascular complications of diabetes and in pancreatic -cell failure in diabetes. Notably, obese people without diabetes also display elevated levels of systemic oxidative stress. In addition, levels of oxidative stress are increased in the adipose tissue in obese mice. Treating obese mice with antioxidant agents attenuates the development of diabetes. In 3T3-L1 adipocytes, increases in reactive oxygen species (ROS) occur with lipid accumulation; the addition of free fatty acids elevates ROS generation further. Thus, adipose tissue represents an important source of ROS; ROS may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. Moreover, the levels of oxidative stress present in several other types of cells or tis-sues, including those in the brain, arterial walls, and tumors, have been implicated in the pathogenesis associated with hypertension, atherosclerosis, and cancer. The increased levels of systemic oxidative stress that occur in obesity may contribute to the obesity-associated development of these diseases.