Combination of low- or moderate-intensity statin and ezetimibe versus high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: A propensity-matched nationwide cohort study.

AIMS: This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting. METHODS AND RESULTS: Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death. Secondary outcome was an individual event. The study population was followed from baseline until the date of events, or the last health check-ups, whichever came first.Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination significantly reduced the risk of composite outcome (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.77-0.92, P < 0.001) as well as individual MI (HR 0.81, 95% CI 0.71-0.94, P = 0.005) and stroke (HR 0.78, 95% CI 0.65-0.93, P = 0.005), but not all-cause death. Low-intensity statin with ezetimibe also significantly reduced the risk of the composite outcomes (HR 0.80, 95% CI 0.66-0.97, P = 0.024) compared to high-intensity statin monotherapy, but the risk of individual outcome did not differ between two groups. Statin and ezetimibe combination demonstrated consistent effect across various subgroups. CONCLUSIONS: Among people without pre-existing CVD, moderate-intensity statin with ezetimibe combination was superior to high-intensity statin monotherapy in preventing composite outcomes as well as each of MI and stroke. In contrast, low-intensity statin with ezetimibe combination reduced the risk of composite but not individual outcomes.

We compared the preventive effect of low- or moderate-statin with ezetimibe combination and high-intensity statin monotherapy on cardiovascular disease and all-cause death.Low- or moderate-intensity statin with ezetimibe is beneficial for reducing a composite of MI, stroke, and all-cause death.Moderate-intensity statin with ezetimibe reduced 19% of MI and 22% of stroke, compared with high-intensity statin.Statin with ezetimibe combination might be attractive bypass for primary prevention, beyond an alternative to high-intensity statin.

Delayed diagnosis of pseudohypoparathyroidism type 1a with rare hypothyroidism since childhood.

Pseudohypoparathyroidism (PHP) is a rare disorder that associates with resistance to parathyroid hormone (PTH). A 21-year old man visited outpatient clinic to treat previously diagnosed hypothyroidism and vitamin D deficiency. Despite daily 150 mcg of levothyroxine supplement, thyroid-stimulating hormone level was elevated, but thyroid autoantibodies were not detected. He showed features of Albright Hereditary Osteodystrophy and elevated serum PTH level with normal albumin-corrected calcium and phosphorus level. The Ellsworth-Howard test proved the blunted response of urinary phosphorus and cyclic adenosine monophosphate after the infusion of the exogenous PTH, suggesting PTH resistance. DNA analysis revealed a heterozygous mutation in the GNAS gene (c.478C > T). Herein, we report a case of PHP type 1a confirmed by clinical, biochemical and molecular analyses. Establishing correct diagnosis of PHP is necessary for efficient therapeutic management.

A rare case of multiple endocrine neoplasia type 1 initially presenting as an asymptomatic, huge mediastinal mass: case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited syndrome that concurrently involves various endocrine glands. We report a rare case of MEN1 in a 43-year-old man whose first manifestation was an asymptomatic mediastinal mass. CASE PRESENTATION: A 13-cm-sized mediastinal mass was diagnosed as an atypical thymic carcinoid by computed tomography and percutaneous needle biopsy. In addition, hypercalcemia from a left inferior parathyroid hyperplasia, and a non-functioning gastric neuroendocrine tumor seen on esophagogastroduodenoscopy were found. Therefore, the patient was clinically diagnosed with MEN1 syndrome, and underwent surgical resection of thymic carcinoid tumor after pre-operative concurrent chemoradiation therapy to decrease tumor size and volume. Parathyroid lesion and gastric neuroendocrine tumor were also removed. Finally, a MEN1 gene mutation was observed in the patient and his 7-year-old son. CONCLUSION: Despite its rare occurrence, thymic carcinoid tumor should be considered as a MEN1-associated tumor and necessitates screening of other endocrine glands. Thymic carcinoid tumor carries a poor prognosis in patients with MEN1, and thus it needs to be carefully monitored even after radical excision.

Compound K attenuates glucose intolerance and hepatic steatosis through AMPK-dependent pathways in type 2 diabetic OLETF rats.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Twenty-four-week-old male OLETF rats were assigned to four groups: control (saline), CK 10 mg/kg, CK 25 mg/kg, or metformin 300 mg/kg (positive control); all treatments were administered orally for 12 weeks. RESULTS: Fasting glucose levels of the CK25 group were significantly lower than those of the control group during the 12 weeks. The results of the oral glucose tolerance test showed that both the glucose concentration after glucose loading and the fasting insulin levels of the CK25 group were significantly lower than those of the control. Hepatosteatosis was significantly improved by CK25. CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK). CK25 significantly inhibited the expression of sterol regulatory element-binding protein-1c and fatty acid synthase, while upregulating that of peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1. CONCLUSIONS: CK improved glucose intolerance and hepatosteatosis in HFD-fed OLETF rats through AMPK activation, which has dual mode of action that involves decreasing the synthesis of fatty acids and increasing fatty acid oxidation.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

Serum bisphenol a concentration in postmenopausal women with osteoporosis.

OBJECTIVES: Bishphenol A (BPA) is a representative endocrine disruptor and is also known as a xenoestrogen. The objective of the present study is to investigate how many patients are exposed to BPA and to analyze the relationships between serum BPA concentration, bone mineral density (BMD) and biochemical bone markers in postmenopausal women with osteoporosis. METHODS: Total 51 patients were enrolled for measuring BPA and clinical variables including BMD and bone markers. The relationship between BPA and clinical variables were analyzed by the Pearson's correlation test and the Kruskal-Wallis test. Serum BPA concentration was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: BPA was detected in all samples. The mean BPA concentration was 1.44 ± 0.52 ng/mL. There was no statistically significant correlation between BPA and clinical variables. CONCLUSION: There was no statistical significance between serum BPA concentration and clinical variables related to bone metabolism. To clarify the effect of BPA on bone metabolism, further large scaled and high risk group investigation may be needed.

Inhibition of NF-κB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells.

Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-κB (NF-κB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-κB activation. Also, we determined whether selective inhibition of NF-κB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-κB or expression of a recombinant adenovirus vector encoding an IκB-α mutant (Ad-IκBαM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-κB activation was determined by immunohistochemical staining, NF-κB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-κB activity. Treatment with inhibitors of NF-κB such as MG132, PDTC or expression of Ad-IκB-αM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-κB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression.

Sonographic appearance of focal fatty infiltration of the pancreas.

We report the sonographic, CT, and MRI findings in a case of focal fatty infiltration of the pancreas. Sonography revealed an echogenic mass in pancreas head. On CT, the mass was hypodense. The mass showed same signal intensity to the surrounding normal pancreas on in-phase T1-weighted MR images and a loss of signal intensity on opposed-phase MR images.

A case of post-pregnancy osteoporosis combined with ankylosing spondylitis.

Post-pregnancy osteoporosis is not a common disease and is hard to diagnosis because their specific situation is post-partum and lactation. It commonly occurs on lumbar spine within a few months after the birth of a patient's first child and it could lead to be fracture after minor trauma. Although its etiology is not clear, it would not be of sufficient magnitude to cause fractures unless the woman already had a substantial decrease in bone mass. Also, it is rare to be combined with ankylosing spondylitis. Ankylosing spondylitis has a higher risk of osteoporosis and vertebral fracture which increased with the duration of disease. We report a case of post-pregnancy osteoporosis with multiple spinal compression fracture in association of ankylosing spondylitis.

Determining the threshold effect of ozone on daily mortality: an analysis of ozone and mortality in Seoul, Korea, 1995-1999.

Many studies have shown a positive association between ambient ozone levels and mortality. Typically, these findings are based on models that assume a linear relationship between log mortality and ozone level. In this study, we adapted generalized additive models in which ozone effects are presumed to occur in three different ways: as a simple linear term, as a cubic natural spline term, and as a combination of two linear terms (a threshold model). We applied these models to daily time-series data for Seoul, Korea for the years 1995-1999 and found that the threshold model always fits best among the three. A 2.6% (95% CI: 1.7-3.5) increase of estimated relative risk (RR) in the total mortality associated with a 21.5 ppb increase of daily 1-h maximum ozone lagged by 1 day was observed by linear Poisson's regression. However, a 3.4% (95% CI: 2.3-4.4) increase in the estimated RR was observed using the threshold model. Adjustments for other ambient pollutants caused little changes to these results; 2.4-2.5% in the linear models and 3.2-3.4% in the threshold models. In addition, the largest difference in the estimated RRs of the linear and threshold models was observed in the summer: 1.9% (95% CI: 0.5-3.3) by the linear model and 3.8% (95% CI: 2.0-5.7) by the threshold model. These findings indicate that the conventional time-series Poisson regression model, which dose not take threshold into consideration, could underestimate the true risk of the ozone effect on daily mortality.