Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update.

Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.

The effect of Ramadan fasting on serum osmolality in diabetic patients.

OBJECTIVE: To observe the changes of osmolarity levels due to fasting in Ramadan among type 2 diabetic patients. METHODS: The observational study was conducted from May 16 to June 3, 2019, at the Istanbul Medeniyet University, Istanbul, Turkey, and comprised adult type 2 diabetic patients of either gender visiting the diabetes outpatient clinics during the holy month of Ramadan. Those fasting were placed in Group A, while those not fasting formed Group B. Anthropometric measurements and medications in use were recorded. Blood samples were taken in the morning and before the evening meal. Serum osmolality was calculated using serum levels of sodium, glucose and blood urea nitrogen. Data was analysed using SPSS 16. RESULTS: Of the 52 patients, 27(52%) were in Group A and 25(48%) were in Group B. Overall, there were 22(42%) females and 30(58%) males. The mean morning serum osmolalities of the two groups were not different (p>0.05). The mean evening serum osmolality was not significantly different than the mean morning osmolality in Group A (p=0.22). In Group B, the mean evening serum osmolality was significantly lower than the mean morning osmolality (p=0.004). No significant difference was found between mean morning and evening serum osmolalities of those taking sodium-glucose cotransporter 2 (p>0.05). CONCLUSIONS: There was no biochemical sign of dehydration with Ramadan fasting in type 2 diabetes mellitus patients. Clinical Trial Number: [NCT04392570] Link: https://clinicaltrials.gov/.

Assessment of subclinical cardiovascular alterations in nonfunctioning adrenal incidentalomas.

BACKGROUND: Adrenal incidentalomas have been associated with increased cardiovascular risk and have a prevalence as high as 10%. This study aims to evaluate carotid- intima media thickness (CIMT), left ventricular mass, and epicardial adipose tissue thickness in nonfunctioning adrenal incidentaloma patients and compare their results with healthy controls. METHODS: Patients who were referred to the endocrinology clinic for adrenal incidentaloma between 2014 and 2019 were assessed with 1 mg dexamethasone suppression test, 24-h urine metanephrines and normetanephrines, plasma aldosterone to renin ratio. Age and gender-matched subjects without an adrenal mass formed the control group. Left ventricular mass, epicardial adipose tissue thickness, and CIMT of both groups were measured. RESULTS: A total of 41 adrenal incidentaloma patients (21 female, 52.5%) and 40 healthy controls (19 female, 46.3%) were included in the study. Patients with adrenal incidentalomas had increased CIMT. No differences were observed in left ventricle mass or epicardial adipose tissue thickness. There was no correlation between CIMT and adenoma size or serum cortisol (p = 0.2 and p = 0.6, respectively). There was a statistically significant correlation between CIMT and age (p = 0.016, r = 0.295). HBA1c (p = 0.001) and age (p = 0.05) were independently associated with CIMT in regression analysis. DISCUSSION: Adrenal incidentaloma patients need to be monitored for cardiac dysfunction. CIMT may be used to evaluate adrenal incidentaloma patients for early cardiovascular risk.

Serologic Testing for Celiac Disease in Graves' Hyperthyroidism: Should We Act Early?

BACKGROUND: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves'Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. MATERIALS AND METHODS: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG - AGA and IgA - AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. RESULTS: Screening 35 patients with GD revealed positive results for IgA-AGA (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. CONCLUSION: Due to possibility of false seropositivity of celiac antibodies in patients with Graves' thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.

The Frequency and Determinants of HbA1c Variability in Type 2 Diabetic Patients.

Aim: Glycated hemoglobin (HbA1c) is an efficient and easy test to evaluate glycemic control of patients with type 2 diabetes (T2DM). This study aims to evaluate HbA1c variability and associated factors in patients with T2DM. Methods: Four hundred four consecutive patients with T2DM who gave consent to participate and who were eligible were included. The inclusion criterion was presence of three or more HbA1c levels in 1 year. A change ≥0.5% in HbA1c was identified as a significant variability in HbA1c in 1 year. Primary endpoint of the study was to identify the factors associated with HbA1c variability. Patients were grouped as (1) without variability, (2) one variability, and (3) more than one variability. Variability frequency and associated factors such as body mass index, smoking, and c-peptide value were assessed. Results: There were 404 patients (45.3% male) with mean age 58.91 ± 10.8 years. Thirty-four patients (8.4%) had no variability, 19 patients (4.7%) had one variability, and 351 patients (86.9%) had more than one variability. Patients only on insulin treatment and patients on both oral antidiabetic agents (OAD) and insulin had higher variability than patients only on OAD (P = 0.002; P < 0.01). Patients with variability had higher HbA1c levels than patients without variability (P < 0.01). A 1% increase in HbA1c had a 4.864-fold (95% confidence interval: 2.360-10.023) increased variability risk. Conclusions: HbA1c variability is seen in 9 of 10 patients with T2DM and higher HbA1c values and poor glycemic control are associated with a higher risk of HbA1c variability.

Endothelial dysfunction in patients with acromegaly and It's association with Endocan.

OBJECTIVE: This study aims to assess endocan levels in patients with acromegaly who have active disease or disease in remission and to investigate a relation between endocan levels and endothelial dysfunction in these patients. DESIGN: The study is a case-control study. Study was conducted at Istanbul Medeniyet University Goztepe Training and Research Hospital between 2013 and 2019. Patients who were older than 18 years with acromegaly diagnosis were recruited if they agreed to participate. Patients with uncontrolled diabetes (DM), hypertension (HT), hyperlipidemia, decompensated heart failure, immune or infectious diseases, moderate-severe valve disease and stage 3 or more advanced chronic kidney disease were excluded. There were 30 healthy control subjects who agreed to participate to the study. Patients with acromegaly were divided into two groups as: disease active patients and patients in remission. Serum endocan levels were measured with enzyme linked immunosorbent assay (ELISA) method endothelial function was assessed with flow mediated dilatation (FMD). RESULTS: There were 85 patients included to the study. Twenty-three patients had active disease, 31 were in remission and 31 were healthy controls. FMD was higher in controls compared to patients in active disease and patients in remission (p < 0.001). There was no difference between patients with active disease for FMD and patients in remission (p = 0.088). There was statistically significant correlation between FMD and endocan and insulin like growth hormone-1 (IGF-1) levels of patients with acromegaly. As FMD increased endocan and IGF-1 decreased. A moderate negative relation between FMD and endocan was identified (p < 0.001, r:-0.409) as well as FMD and IGF-1 levels (p:0.011, r:-0.377). Along with endocan and IGF-1, DM, HT, sex, body mass index, age and uric acid were associated with changes in FMD. CONCLUSIONS: Endocan levels and endothelial function measured with FMD have an inverse relationship. Endocan may prove to be a marker for endothelial dysfunction in acromegaly.

Long-term exposure to outdoor and household air pollution and blood pressure in the Prospective Urban and Rural Epidemiological (PURE) study

Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35­70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 µg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 µg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 µg/m3) compared to the first (PM2.5 < 14 µg/m3) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (ß = 2.15 mmHg, 95% CI: −0.59, 4.89) and diastolic BP (ß = 1.35, 95% CI: −0.20, 2.89), while there was no overall increase in ORs across the full exposure distribution. Individuals who used solid fuels for cooking had lower BP measures compared to clean fuel users (e.g. 34% of solid fuels users compared to 42% of clean fuel users had hypertension), and even in fully adjusted models had slightly decreased odds of hypertension (OR = 0.93; 95% CI: 0.88, 0.99) and reductions in systolic (−0.51 mmHg; 95% CI: −0.99, −0.03) and diastolic (−0.46 mmHg; 95% CI: −0.75, −0.18) BP. In this large international multi-center study, chronic exposures to outdoor PM2.5 was associated with increased BP and hypertension while there were small inverse associations with HAP.

Long-term exposure to outdoor and household air pollution and blood pressure in the Prospective Urban and Rural Epidemiological (PURE) study.

Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35-70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 µg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 µg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 µg/m3) compared to the first (PM2.5 < 14 µg/m3) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (ß = 2.15 mmHg, 95% CI: -0.59, 4.89) and diastolic BP (ß = 1.35, 95% CI: -0.20, 2.89), while there was no overall increase in ORs across the full exposure distribution. Individuals who used solid fuels for cooking had lower BP measures compared to clean fuel users (e.g. 34% of solid fuels users compared to 42% of clean fuel users had hypertension), and even in fully adjusted models had slightly decreased odds of hypertension (OR = 0.93; 95% CI: 0.88, 0.99) and reductions in systolic (-0.51 mmHg; 95% CI: -0.99, -0.03) and diastolic (-0.46 mmHg; 95% CI: -0.75, -0.18) BP. In this large international multi-center study, chronic exposures to outdoor PM2.5 was associated with increased BP and hypertension while there were small inverse associations with HAP.

Psychiatric symptom rate of patients with Diabetes Mellitus: A case control study.

AIMS: The aim of the study is comparing the psychiatric symptom in Type1 DM, Type 2 DM and controls. METHODS: The study was designed as case control study and conducted between September 2011 and April 2012 to the Diabetes Clinic. Age, gender and education level matched 70 type 1 diabetics, 68 type 2 diabetics and 70 controls included to the study. SCL-90-R [Symptom Check List-90 (Revised)] test is used for determining the psychiatric symptom rates. RESULTS: It was found that the rate of somatization, interpersonal sensitivity, anger-hostility and additional scales were significantly different in type 1, type 2 diabetics and controls ((p = 0.023, p = 0.008, p = 0.018 and p = 0.039, respectively). Compared to control group, being a patient with type 1 or type 2 Diabetes found as a risk factor for somatization, depression, anger-hostility and additional scales. Moreover being a patient with type 1 DM was found as a risk factor for having OBS symptoms (p = 0.039) and type 1 DM was protective against having interpersonal sensitivity symptoms (p = 0.006). CONCLUSION: In diabetic patient groups, an increase in the rate of psychiatric symptoms was observed. Therefore a careful psychiatric examination is required in DM.

The Influence of On-pump Versus Off-pump Surgery on Short- and Medium-term Postoperative Coronary Flow Reserve After Coronary Artery Bypass Grafting.

BACKGROUND: Although several clinical trials have compared surgical outcomes between off-pump and on-pump coronary artery bypass grafting (CABG), whether there is a difference in the early- and medium-term postoperative coronary microvascular functions is not fully understood. We compared short- and medium-term coronary microvascular function after off-pump and on-pump CABG. METHODS: A prospective study of patients undergoing off-pump and on-pump CABG. Eighty-two patients scheduled for CABG were recruited: 38 underwent off-pump surgery and 44 on-pump surgery. Each participant's coronary flow reserve (CFR) and diastolic function were measured with transthoracic Doppler echocardiography six and 12 months after surgery. RESULTS: Baseline and hyperaemic diastolic peak flow velocity in the left anterior descending artery were similar in both groups, as was CFR (2.22±0.66) in the off-pump group compared with (2.13±0.61) in the on-pump group, (P=0.54). Coronary flow reserve was significantly and inversely correlated with high sensitivity C-reactive protein concentration (r=-0.416; P<0.001) and positively correlated with mitral E/A-wave velocity ratio (r=0.247; P=0.02). Stepwise linear regression analysis revealed that only high sensitivity C-reactive protein concentration was independently correlated with CFR (ß=-0.272, P=0.02). CONCLUSIONS: Heart-lung bypass technique had no medium-term influence on the coronary microcirculation, despite a possible initial unfavourable effect. Serum hs-CRP concentration was an independent predictor of medium-term coronary microvascular dysfunction.

Impaired Gallbladder Motility and Increased Gallbladder Wall Thickness in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Along with the increase in the incidence of NAFLD and associated obesity, an increase in gallbladder disease (GD) has been noted. This has led to the identification of a new disease entity called fatty GD. There is a gap in the literature on the dynamics of gallbladder function in patients with NAFLD. METHODS: An observational case-control study, a total of 50 patients with biopsy proven NAFLD without gallbladder stone/sludge and 38 healthy comparison subjects were enrolled. Fasting, postprandial gallbladder volumes (PGV), gallbladder ejection fraction (GEF), and fasting gallbladder wall thickness (FGWT) were measured by real-time 2-dimensional ultrasonography. RESULTS: Fasting gallbladder wall thickness, fasting gallbladder volumes and PGV were significantly higher in patients with NAFLD than control subjects (P < 0.001, P = 0.006, and P < 0.001, respectively). Gallbladder ejection fraction was significantly lower in the NAFLD group than the controls (P = 0.008). The presence of NAFLD was an independent predictor for GEF, PGV, and FGWT. Also, steatosis grade was an independent predictor for GEF, and GEF was significantly lower in the nonalcoholic steatohepatitis (NASH) subgroup than the controls. CONCLUSIONS: Gallbladder dysfunction and increase in gallbladder wall thickness exists in asymptomatic (without stone/sludge and related symptoms) patients with NAFLD and are useful in identifying fatty GD. Measurement of these variables in NAFLD patients may be useful in identifying those at higher risk for GD.

A potential treatment of non-alcoholic fatty liver disease with SIRT1 activators.

Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.

Does gestational diabetes history increase epicardial fat and carotid intima media thickness?

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that has begun during pregnancy. Recent studies have proven that development of atherosclerosis may be established in this population even without presence of type 2 diabetes. For assessment of atherosclerosis, epicardial fat thickness (EFT) is recently being used as a surrogate marker. In this study, we aimed to prove that women with GDM history are more inclined to have higher EFT levels than women without GDM history. METHODS: Sixty-two patients with previous GDM and 33 age- and sex-matched controls were allocated. Epicardial fat thicknesses of the subjects were measured with transthorasic echocardiography and carotid intima media thickness (c-IMT) was measured with ultrasound. Insulin resistance (IR) of each subject was assessed with Homeostasis model of assessment-insulin resistance (HOMA-IR). RESULTS: Carotid IMT and EFT were significantly higher in previous GDM group than controls. Serum gamma-glutamyl transferase (GGT), uric acid, and high-sensitivity C-reactive protein (hs-CRP) levels were also found significantly higher in the patients with previous GDM as compared to the controls. We observed that carotid IMT (ß = 310, P = 0.003), total cholesterol (ß = 315, P = 0.002), BMI (ß = 308, P = 0.002), HbA1c (ß = 227, P = 0.018), and HOMA-IR (ß = 184, P = 0.049) were independently correlated with EFT. CONCLUSIONS: Although the number of patients included in this study is limited, high EFT results may indicate presence of atherosclerosis in women with previous GDM.