Congenital Adrenal Hyperplasia with Combined 21-hydroxylase deficiency and 17α-hydroxylase/17,20-lyase deficiency: An undervirilized male.

21-hydroxylase deficiency stands as the most prevalent form of congenital adrenal hyperplasia, primarily resulting from mutations in the CYP21A2 gene. On the other hand, mutations within the CYP17A1 gene lead to 17α-hydroxylase/17,20-lyase enzyme deficiencies. The scarcity of 17-OH deficiency is noteworthy, accounting for less than 1% of all congenital adrenal hyperplasia cases. The male patient, born from a first-degree cousin marriage, exhibited several symptoms, including left undescended testis, micropenis, penile chord, left sensorineural hearing loss, and gynecomastia. He reported micropenis as a concern at the age of 13.5 years. His hormone profile revealed high levels of serum 17-hydroxyprogesterone, progesterone, and pregnenolone. In this case with a 46 XY karyotype, suspicions arose regarding Cytochrome P450 oxidoreductase deficiency due to ambiguous genitalia and an atypical hormone profile. Analysis unveiled two distinct homozygous and pathogenic variants in the CYP21A2 and CYP17A1 genes. Notably, mineralocorticoid precursors escalated, while cortisol and sex steroid precursors decreased during the high (250 mcg) dose ACTH stimulation test. The mutation c.1169C > G (p.Thr390Arg) in CYP17A1, which is the second documented case in literature, stands out due to its unique set of accompanying features. Mutations occurring in CYP21A2 and CYP17A1 result in complete or partial enzyme deficiencies, and the detection of homozygous mutations in two different enzyme systems within the steroidogenic pathway is noteworthy.

Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants.

Human Inborn Errors of Immunity (IEIs) encompass a clinically and genetically heterogeneous group of disorders, ranging from mild cases to severe, life-threatening types. Among these, Primary Immune Regulatory Disorders (PIRDs) constitute a subset of IEIs characterized by diverse clinical phenotypes, prominently featuring severe atopy, autoimmunity, lymphoproliferation, hyperinflammation, autoinflammation, and susceptibility to malignancies. According to the latest report from the International Union of Immunological Societies (IUIS), PIRDs arise from mutations in various genes including LYST, RAB27A, AP3B1, AP3D1, PRF1, UNC13D, STX11, STXBP2, FAAP24, SLC7A7, RASGRP1, CD70, CTPS1, RLTPR, ITK, MAGT1, PRKCD, TNFRSF9, SH2DIA, XIAP, CD27 (TNFRSF7), FAS (TNFRSF6), FASLG (TNFSF6), CASP10, CASP8, FADD, LRBA, STAT3, AIRE, ITCH, ZAP70, TPP2, JAK1, PEPD, FOXP3, IL2RA, CTLA4, BACH2, IL2RB, DEF6, FERMT1, IL10, IL10RA, IL10RB, NFAT5, TGFB1, and RIPK1 genes. We designed a targeted next-generation sequencing (TNGS) workflow using the Ion AmpliSeq™ Primary Immune Deficiency Research Panel to sequence 264 genes associated with IEIs on the Ion S5™ Sequencer. In this study, we report the identification of 38 disease-causing variants, including 16 novel ones, detected in 40 patients across 15 distinct PIRD genes. The application of next-generation sequencing enabled rapid and precise diagnosis of patients with PIRDs.

Diagnosing Alström syndrome in a patient followed up with syndromic obesity for years.

Alström syndrome (AS) is a rare autosomal recessive monogenic disorder caused by mutations of the Alström syndrome 1 (ALMS1) gene, located on chromosome 2p13. It is a progressive multisystemic disease characterized mostly by obesity, sensorineural hearing loss, visual impairments, cardiomyopathy, insulin resistance and/or type 2 diabetes mellitus (T2DM), metabolic dysfunctions, non-alcoholic fatty liver disease, and chronic progressive kidney disease. Generally, the first clinical symptoms of the disease appear in the first years of life with a major variation of onset age. In this study, we aimed to examine the molecular diagnosis of a 6-year-old patient with suspected AS clinical symptoms. After applying clinical exome sequencing (CES) in the patient we found a homozygous deletion in exon 8 at the ALMS1 gene (c.2311_2312del). We identified a homozygous frameshift mutation. The reported variant was pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG). Thus, the patient was diagnosed with AS as a result of the combined clinical phenotype and genetic tests results. We hope the variant we found can expand the spectrum of ALMS1 variants in AS.

The effect of the COVID-19 pandemic on metabolic control in children with type 1 diabetes: a single-center experience.

OBJECTIVES: Coronavirus disease 2019 has caused a major epidemic worldwide, and lockdowns became necessary in all countries to prevent its spread. This study aimed to evaluate the effects of staying-at-home practices on the metabolic control of children and adolescents with type 1 diabetes during the pandemic period. MATERIALS AND METHODS: Eighty-nine patients younger than 18 years old who were diagnosed with type 1 diabetes at least one year before the declaration of the pandemic were included in the study. The last visit data of the patients before and after the declaration of the pandemic, and the frequency of presentation of diabetes-related emergencies from one year after diagnosis of type 1 diabetes to the declaration of the pandemic, and from the declaration of the pandemic to the last visit after the pandemic declaration were compared. RESULTS: The total number of patients was 89, and 48 (53.9%) were boys. The mean (± standard deviation [SD]) age at diagnosis was 8.4 ± 3.7 years (boys 7.9 ± 3.6 years; girls 8.9 ± 3.9 years). There was no statistically significant difference when the SD values of the anthropometric measurements, and the glycosylated hemoglobin (HbA1c) and lipid profile tests were compared. However, the frequency of admission to the emergency service related to diabetes was significantly different. CONCLUSIONS: Although the pandemic did not significantly affect the metabolic and glycemic controls of the children with type 1 diabetes included in this study, an increase in the frequency of diabetes-related emergency admissions was noted.

The relationship between paraoxonase-1 activity and coronary artery disease in patients with metabolic syndrome.

OBJECTIVES: We investigated the correlation of serum paraoxonase-1 (PON-1) activity with coronary artery disease (CAD) in patients with metabolic syndrome (MetS). STUDY DESIGN: The study included 21 patients (mean age 55 ± 9 years) with MetS, stable angina pectoris, and angiographically shown CAD, 24 patients (mean age 51 ± 10 years) with MetS and angiographically normal coroner arteries, and 28 healthy controls (mean age 49 ± 12 years). Demographic and clinical characteristics, insulin levels, homeostasis model assessment of insulin resistance index, and PON-1 activity were assessed in all the groups. Severity of CAD was assessed using the Gensini score. RESULTS: Paraoxonase-1 activity was significantly lower in patients with MetS compared to the control group (p=0.02). The two MetS groups with and without CAD exhibited similar characteristics in all the parameters including PON-1 activity (p>0.05). Univariate correlation analysis performed in MetS-CAD patients showed a significant negative correlation between the Gensini score and PON-1 activity (r=-0.48, p=0.02). The overall PON-1 activity of all the subjects showed no correlation with the parameters examined. CONCLUSION: Decreased PON-1 activity in patients with MetS compared to the control group suggests increased oxidative stress in MetS. Detection of similar PON-1 activity levels in MetS groups with and without CAD suggests that disturbance of oxidative-antioxidative balance occurs before the development of CAD. The negative correlation between the Gensini score and PON-1 activity implies that decreased PON-1 activity may be one of the etiologic causes of atherosclerotic progress in MetS.

Broad-spectrum XX and XY gonadal dysgenesis in patients with a homozygous L193S variant in PPP2R3C.

CONTEXT: Homozygous and heterozygous variants in PPP2R3C are associated with syndromic 46,XY complete gonadal dysgenesis (Myo-Ectodermo-Gonadal Dysgenesis (MEGD) syndrome), and impaired spermatogenesis, respectively. This study expands the role of PPP2R3C in the aetiology of gonadal dysgenesis (GD). METHOD: We sequenced the PPP2R3C gene in four new patients from three unrelated families. The clinical, laboratory, and molecular characteristics were investigated. We have also determined the requirement for Ppp2r3c in mice (C57BL6/N) using CRISPR/Cas9 genome editing. RESULTS: A homozygous c.578T>C (p.L193S) PPP2R3C variant was identified in one 46,XX girl with primary gonadal insufficiency, two girls with 46,XY complete GD, and one undervirilised boy with 46,XY partial GD. The patients with complete GD had low gonadal and adrenal androgens, low anti-Müllerian hormone, and high follicle-stimulating hormone and luteinizing hormone concentrations. All patients manifested characteristic features of MEGD syndrome. Heterozygous Ppp2r3c knockout mice appeared overtly normal and fertile. Inspection of homozygous embryos at 14.5, 9.5, and 8.5 days post coitum(dpc) revealed evidence of dead embryos. We conclude that loss of function of Ppp2r3c is not compatible with viability in mice and results in embryonic death from 7.5 dpc or earlier. CONCLUSION: Our data indicate the essential roles for PPP2R3C in mouse and human development. Germline homozygous variants in human PPP2R3C are associated with distinctive syndromic GD of varying severity in both 46,XY and 46,XX individuals.

Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche.

BACKGROUND: We aimed to evaluate the clinical follow-up data of patients with premature thelarche and determine the rate of development of precocious and early puberty in these patients. METHODS: The charts of 158 girls with premature thelarche who were followed-up in our pediatric endocrinology polyclinic were reviewed. The patients were divided into three groups according to the age at onset: group 1 (0-1 month) (n=12), group 2 (1-24 months) (n=40) and group 3 (2-8 years) (n=106). RESULTS: At admission, the mean height standard deviation score (SDS), body weight (BW)-SDS, body mass index (BMI) and BMI-SDS were significantly higher in group 3 than in group 1 and group 2. At admission, 8.8% of the patients were obese and 24% of the patients were overweight. The majority of patients who were obese and overweight were in group 3. At the end of the follow-up, thelarche regressed in 24.7%, persisted in 32.9%, progressed in 25.9% and had a cyclic pattern in 16.5% of the patients. Precocious or rapidly progressive puberty developed in 47 of the 158 patients (29.7%). The mean age at progression to early or rapidly progressive puberty was 98.1±17.6 months. A total of 89.3% of the patients who progressed to early or rapidly progressive puberty were in group 3. CONCLUSIONS: Precocious or rapidly progressive puberty developed in 29.7% of subjects with premature thelarche. As patients who developed rapidly progressive puberty had a higher BW-SDS and BMI-SDS than those who did not, it is suggested that the increase in weight could stimulate rapidly progressive puberty in cases with premature thelarche.

Coronary angioplasty induced oxidative stress and its relation with metoprolol use and plasma homocysteine levels.

OBJECTIVE: Short episodes of myocardial ischemia during coronary angioplasty may induce oxidative stress and increase lipid peroxidation. The aim of this study was to determine the effect of metoprolol on lipid peroxidation by measurements of malondialdehyde (MDA) and total antioxidant capacity (TRAP) in patients undergoing angioplasty. The relations between homocysteine level and lipid peroxidation were also studied. METHODS: Forty-six patients (mean age 57 years, 37 males) undergoing elective angioplasty were enrolled. Metoprolol treatment was initiated in 27 patients (group 1), meanwhile 19 patients could not take metoprolol due to diverse contraindications (group 2). RESULTS: Following angioplasty, while venous MDA levels decreased in group 1 (0.188+/-0.021 vs. 0.159+/-0.020 nmol/ml, p=0.05), an increase was detected in group 2 (0.203+/-0.025 vs. 0.229+/-0.024 nmol/ml, p=0.045) as compared with baseline levels. In group 1, TRAP levels markedly increased after angioplasty in venous samples (1.201+/-0.036 vs. 1.478+/-0.044 mmol/L, p=0.0001). However, small increase was observed for TRAP in group 2 (1.274+/-0.043 vs. 1.363+/-0.053 mmol/L, p=0.05). There was no significant change in plasma homocysteine levels with angioplasty. There was no significant correlation between homocysteine, changes in MDA and TRAP levels either. CONCLUSION: Administration of metoprolol may cause a reduction in the oxidative stress and an increase in the antioxidant activity in patients undergoing elective angioplasty.

Apolipoprotein E polymorphism in diabetic and non-diabetic patients: does it really contribute to atherosclerosis?

OBJECTIVE: The exact mechanism of the increased cardiovascular morbidity and mortality in type-2 diabetes is still undefined. The aim of our study was to assess the impact of apolipoprotein E (apo E) polymorphism and other factors on atherosclerotic vascular disease in type-2 diabetic patients. We also examined the association between apo E polymorphism and lipid profile in diabetic patients. METHODS AND RESULTS: We assessed the apo E polymorphism in 295 atherosclerotic patients (124 of them had diabetes (according to WHO criteria) and 171 of them had coronary artery narrowing > 50). The detection of apo E polymorphism was made by Real-Time PCR using a Light-Cycler (Roche diagnostics, GmbH, Mannheim, Germany). Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lipoprotein (a) [Lp(a)], apolipoprotein A (Apo A) and apolipoprotein B (Apo B) levels were determined by biochemical analyser. Genotypic distribution of apo E polymorphism did not differ between diabetic and non-diabetic atherosclerotic patients. The distributions of apo E2/2, E2/3, E2/4, E3/3, E3/4 and E4/4 genotypes in diabetic and non-diabetic atherosclerotic patients were 7.3%: 8.2%, 15.3%: 15.8%, 4.0%: 5.3%, 50.8%: 56.7%, 16.9%: 11.1% and 5.6%: 2.9%, respectively. Participants were grouped as apo E2 (E2/2 or E2/3), apo E3 (E3/3), or apo E4 (E4/4 or E4/3). The distributions of apo E2, E3 and E4 alleles were 23.5%, 52.9%, 23.5%, for diabetic patients, and 25.3%, 59.9%, 14.8% for non-diabetic patients, respectively. The apolipoprotein E genotype was not associated with the lipid levels in diabetic patients. CONCLUSIONS: Our findings imply that apo E polymorphism is not related to the development of atherosclerosis in patients with type-2 diabetes.

Impact of invasive strategy for the management of patients with cardiogenic shock after acute myocardial infarction.

OBJECTIVE: This study evaluates the influence of early revascularization (with percutaneous transluminal coronary angioplasty (PTCA) and coronary surgery) on short- and long-term survival in patients with cardiogenic shock complicating acute myocardial infarction (AMI). METHODS AND RESULTS: In-hospital and 6-month survival were retrospectively determined on day 193 (65-270, median +/- 25th and 75th percentiles) in 87 patients who either underwent early invasive reperfusion (group A, n=60) or those who were treated conservatively (group B, n=27). In-hospital mortality was 37% in group A and 56% in group B (P=0.192). Six-month mortality was statistically lower in group A than in group B (30 patients (50%) compared with 25 patients (93%), P=0.005). Being a woman and older age were found to be factors increasing mortality. Lower mortality in the long term was strongly associated with revascularization (odds ratio=0.08, 95% confidence interval=1.54-109). PTCA was found to be an independent predictor of long-term survival (odds ratio= 0.22, 95% confidence interval=0.049-1.00, P=0.050), by multiple logistic regression. CONCLUSIONS: In conclusion, this study suggests that early revascularization improves long-term survival of patients with cardiogenic shock complicating AMI, even after adjustment for baseline differences between patients who underwent early revascularization and those who did not.

Elevated plasma endothelin-1 levels in coronary sinus during rapid right atrial pacing in patients with slow coronary flow.

The aim of the study was to evaluate whether there was an imbalance between endothelin-1 (ET-1) and nitric oxide (NOx) release and diffuse atherosclerotic changes existed in patients with slow coronary flow (SCF). Baseline and post-atrial pacing coronary sinus ET-1 and NOx levels were measured in 19 patients with SCF (11 female, 56 +/- 9 years) and in 14 control subjects (nine female, 54 +/- 7 years). All patients underwent subsequent intravascular ultrasound (IVUS) investigation at the same setting with right atrial pacing. Baseline arterial (12.4 +/- 9.9 vs. 6.3 +/- 5.1 pg/ml, P<0.005) and coronary sinus (12.2 +/- 11.1 vs. 6.4 +/- 6.9 pg/ml, P<0.005) ET-1 plasma levels were higher in patients than in controls. After atrial pacing, concentration of ET-1 level from coronary sinus (24.7 +/- 14.6) significantly increased as compared to baseline (12.4 +/- 9.9, P<0.0001) and control levels (5.3 +/- 6.3, P<0.0001). Additionally, coronary sinus ET-1 level increased significantly with atrial pacing compared to femoral artery ET-1 level (16.3 +/- 8.5, P<0.005) in patients with SCF. After atrial pacing, the femoral artery ET-1 level also increased in patients compared to control level (P<0.0001). No significant differences in arterial and coronary sinus NOx plasma levels were found between the two groups, both at baseline and after pacing. Upon IVUS investigation, the common finding was longitudinally extended massive calcification throughout the epicardial arteries in patients with SCF. Mean intimal thickness was 0.59 +/- 0.18 mm. The data of this study suggest that increased ET-1 levels and insufficient NOx response, as well as the pathological data of IVUS may be associated with coronary microvascular dysfunction and may be the manifestation of early diffuse epicardial atherosclerosis in these patients with SCF.

Increased incidence of carotid artery wall changes and associated variables in hemodialysis patients without symptomatic cardiovascular disease.

Cardiovascular disease (CVD) is still the major cause of the morbidity and mortality in hemodialysis (HD) patients. The characteristics of major arterial changes, atherosclerosis and related risk factors in HD patients remain unclear. We aimed to evaluate the atherosclerotic process in asymptomatic HD patients and healthy volunteers, and to determine the association between the risk factor(s) and the atherosclerotic process in these groups. 92 HD patients (female: 43, male: 49) and 62 age and sex matched healthy volunteers (female: 27, male: 35) were enrolled in this study. Diabetics, smokers, and patients with symptomatic CVD were excluded. The right and left carotid intima-media thicknesses (CIMTs) were measured and plaque structures were studied by B-mode ultrasound. The mean CIMT in patients and control group were 0.79 +/- 0.16 mm and 0.54 +/- 0.09 mm, respectively. Mean CIMT in HD patients was thicker (p < 0.001) and the presence ratio of plaque was higher in patients group (n=38, %61.2 vs n=9, %17.3) (p < 0.001). Calcified type of plaque was more frequent in HD patients than control group. Age (r=0.48, p < 0.001), left ventricular mass (r=0.42, p < 0.05), and homocysteine (r=0.46, p < 0.01), mean hematocrit (r=-0.36, p < 0.05), plasma CRP (r=0.50, p < 0.001), ESR (r=0.43, p < 0.01) and albumin (r= -0.34, p < 0.05) levels were correlated with the CIMT measurements and plaque presence, significantly. -CIMT as an atherosclerotic process indicator is thicker in asymptomatic HD patients than healthy subjects. We concluded that in addition to various classical risk factors, uremic environment may also contribute to acceleration of the atherosclerotic process.

Familial hypertrophic cardiomyopathy complicated by complete atrioventricular block.

We described a patient with familial non-obstructive hypertrophic cardiomyopathy and complete atrioventricular block. A 27-year-old male was admitted to our institution with syncope. Electrocardiography demonstrated complete atrioventricular block. Two-dimensional echocardiography revealed non-obstructive hypertrophic cardiomyopathy. A temporary transvenous ventricular pacemaker was inserted urgently, and subsequently replaced by a permanent dual-chamber pacemaker. Meanwhile, non-obstructive hypertrophic cardiomyopathy was diagnosed in the mother, the aunt and one of the brothers of the patient in the screening of the family, but atrioventricular conduction block was not detected in them. In the electrophysiological study of the mother, inducible ventricular tachycardia was detected. The reason for diversity of the arrhythmias in the members of the same family with hypertrophic cardiomyopathy may be explained by penetrance. The phenotype of the familial hypertrophic cardiomyopathy is influenced by factors varying the penetrance, such as age and gender.

Slow coronary flow may be a sign of diffuse atherosclerosis. Contribution of FFR and IVUS.

OBJECTIVE: Slow coronary flow (SCF) is a phenomenon characterized by delayed opacification of coronary arteries in the absence of epicardial occlusive disease, in which many aetiological factors such as microvascular and endothelial dysfunction, and small vessel disease have been implicated. We aimed to investigate the epicardial resistance in relation with SCF by using fractional flow reserve (FFR) and intravascular ultrasound (IVUS). Both have been combined to disclose the related epicardial flow resistance and the arterial anatomy. METHODS AND RESULTS: Coronary pressure and FFR measurement were performed in 19 (8 (42.1%) men, 11 (57.9%) women; age = 55.9 +/- 9.4 years) patients with SCF. All patients underwent subsequent IVUS investigation at the same setting. As compared with expected normal values, FFR values were significantly lower (1.0 vs. 0.83 +/- 0.13, p < 0.0001). In patients with SCF, a strong negative correlation was seen between TIMI frame count and FFR (r = -0.551, p < 0.05). Upon IVUS investigation, the common finding was longitudinally extended massive calcification throughout the epicardial arteries and increased intimal thickness (0.59 +/- 0.18 mm). A negative correlation between intimal thickness and FFR was determined (r = -467, p < 0.05). CONCLUSION: We have demonstrated the decreased FFR in the patients with SCF. Decreased FFR levels have been attributed to increased resistance in the epicardial coronary arteries due to diffuse atherosclerotic disease which has been demonstrated by IVUS.

Effects of atrial pacing on coronary sinus endothelin-1 and nitric oxide levels in patients with myocardial bridging.

Myocardial bridging (MB) is associated with clinical and metabolic evidence of ischaemia. In the present study, we aimed to evaluate the extent of atherosclerosis and endothelial dysfunction in patients with MB. The study population consisted of 15 patients with MB [9 women (60%), aged 56 +/- 9 years] and 14 control subjects [8 women (57%), aged 54 +/- 10 years]. All patients underwent coronary angiography. The femoral artery and coronary sinus endothelin-1 (ET-1) and nitric oxide (NOx) plasma levels were measured before and after right atrial pacing in all subjects. Also, intravascular ultrasonography was performed in 13 patients with MB. With right atrial pacing, coronary sinus ET-1 levels increased significantly in patients with MB compared with baseline levels (5.77 +/- 6.76 versus 11.32 +/- 9.40 pg/ml, p < 0.05). The coronary sinus ET-1 levels remained unchanged in controls with pacing (3.99 +/- 4.00 versus 4.19 +/- 7.15 pg/ml, p > 0.05). There was no significant difference between the two groups according to the increase in NOx levels with atrial pacing. Ten (77%) of the 13 patients had plaque formation in the segments proximal to the bridge with an area stenosis of 37 +/- 21% (12% to 75%). In patients with MB, post-pacing levels of coronary sinus ET-1 correlated significantly with the cross-sectional area of the plaque (r = 0.65, p = 0,04). Increased ET-1 levels and the pathological data of intravascular ultrasonography may be associated with endothelial dysfunction and atherosclerosis development in patients with MB. The presence of atherosclerosis in the proximal segments to the bridge may contribute to the myocardial ischaemia detected in these patients.

[Femoral vascular complications after percutaneous coronary interventions]. / Perkütan koroner girisimler sonrasi femoral vasküler komplikasyonlar.

OBJECTIVE: We aimed to investigate peripheral vascular complications and their relation with treatment and clinical parameters in percutaneous transluminal coronary angioplasty (PTCA) patients. METHODS: We included into the study 321 patients (aged 57+/-11 years) underwent PTCA between November 2001-August 2002. The age, gender, glycoprotein 2b/3a use, thrombolytic use, intraaortic balloon treatment, transient pacemaker treatment, reintervention history, hypertension, diabetes mellitus, smoking status, family history and the correlations of these parameters with local vascular complications were assessed in all patients. RESULTS: Pseudoaneurysm incidence was significantly correlated with; age [(n=13, 68.0%) p=0.0001, OR 8.38], female gender [(n=12, 63.1%) p<0.015, OR 0.32], reintervention [(n=10, 52.1%) p<0.004, OR 3.6], venous sheath usage [(n=12, 63%) p<0.0001, OR 9.07], thrombolytic treatment [(n=5, 26.3%) p<0.0001, OR 7.9], and intraaortic balloon adjustment [(n=6, 31.5%) p<0.0001, OR 7.2]. No correlation was found between pseudoaneurysm incidence and glycoprotein 2b/3a treatment, smoking, diabetes mellitus, hypertension and family history. CONCLUSION: The present study showed that patients of female gender, with reintervention, thrombolytic treatment, venous sheath use and intraaortic balloon adjustment are at high risk for serious femoral vascular complications, especially when they are aged. Additionally, glycoprotein 2b/3a agents can be used without increased risk of peripheral vascular complications.

Plasma homocysteine is associated with ischemic findings without organic stenosis in patients with slow coronary flow.

AIM: To investigate the plasma concentrations of homocysteine (Hcy) in slow coronary flow (SCF) patients before and at the end of the exercise test and compare with the values of healthy controls. METHODS: Study population consisted of 41 patients with SCF [68% men, aged 49 ± 8 years], and 41 subjects with normal epicardial coronary arteries [56% men, aged 50 ± 9 years]. Exercise test was performed in all study participants. Blood samples were drawn at rest and immediately at the end of exercise testing after 12h of overnight fasting. RESULTS: The baseline Hcy value of the SCF patients was higher than that of the control subjects (p<0.0001), and this difference continued after exercise test between the groups (p<0.0001). Median post-exercise increases in Hcy levels were higher in the SCF group than in the control group, without a significant difference (p=0.088). In the SCF group after exercise, Hcy levels in 17 patients with angina and 18 patients with ST depression were higher than those without angina and ST depression (p<0.0001 and p<0.0001, respectively). In addition, Hcy values in patients with both angina and ST depression were greater than those with either angina (p<0.05) or ST depression (p<0.05). CONCLUSION: The results of this study show that there is an important pathophysiologic link between the increased levels of plasma Hcy, the degree of ischemic findings, and the severity of slow flow in SCF patients.

NT-Pro-BNP levels and their response to exercise in patients with slow coronary flow.

BACKGROUND: Natriuretic peptides are released by the heart in response to wall stress. OBJECTIVE: The NT-Pro-BNP concentrations in slow coronary flow (SCF) patients were assessed before and after the exercise test and compared with the values of healthy controls. METHODS: The study population was 34 patients with SCF [22 males (64.7%), aged 51.0 ± 6.2 years], and 34 normal subjects with normal coronary arteries [21 males (61.8%), aged 53.2 ± 6.6 years]. Coronary flow rates of all patients and control subjects were documented as Thrombolysis in Myocardial Infarction (TIMI) frame count. Blood samples were drawn at rest and after the exercise testing. RESULTS: The baseline NT-Pro-BNP concentrations of the SCF patients were higher than those of the control subjects (NT-Pro-BNP: 49.7 ± 14.2 pg/mL vs. 25.3 ± 4.6 pg/mL p<0.0001, respectively), and this difference increased after exercise test between the groups (NT-Pro-BNP: 69.5 ± 18.6 pg/mL vs. 30.9 ± 6.4 pg/mL p<0.0001). In SCF group after exercise, NT-Pro-BNP concentration in 15 patients with angina was higher than those without angina (76.8 ± 17.8 pg/mL vs. 63.8 ± 17.5 pg/mL p=0.041). NT-Pro-BNP concentration in 11 patients with ST depression was also higher than those without ST depression (82.4 ± 17.3 pg/mL vs. 63.3 ± 16.1 pg/mL p=0.004). Median post-exercise increases in NT-Pro-BNP (Δ NT-Pro-BNP) were higher in the SCF group than in the control group (Δ NT-Pro-BNP: 19.8 ± 7.7 pg/mL vs. 5.7 ± 4.5 pg/mL p<0.0001). CONCLUSION: The results of this study suggest that there may be an important pathophysiologic link between the severity of SCF (microvascular or epicardial coronary artery dysfunction) and the level of circulating NT-Pro-BNP in SCF patients.

The distribution of circulating microRNA and their relation to coronary disease.

BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression by suppressing protein translation and may influence RNA expression. MicroRNAs are detected in extracellular locations such as plasma; however, the extent of miRNA expression in plasma its relation to cardiovascular disease is not clear and many clinical studies have utilized array-based platforms with poor reproducibility. METHODS AND RESULTS: Initially, to define distribution of miRNA in human blood; whole blood, platelets, mononuclear cells, plasma, and serum from 5 normal individuals were screened for 852 miRNAs using high-throughput micro-fluidic quantitative RT-PCR (qRT-PCR). In total; 609, 448, 658, 147, and 178 miRNAs were found to be expressed in moderate to high levels in whole blood, platelets, mononuclear cells, plasma, and serum, respectively, with some miRNAs uniquely expressed. To determine the cardiovascular relevance of blood miRNA expression, plasma miRNA (n=852) levels were measured in 83 patients presenting for cardiac catheterization. Eight plasma miRNAs were found to have over 2-fold increased expression in patients with significant coronary disease (≥70% stenosis) as compared to those with minimal coronary disease (less than 70% stenosis) or normal coronary arteries. Expression of miR-494, miR-490-3p, and miR-769-3p were found to have significantly different levels of expression. Using a multivariable regression model including cardiovascular risk factors and medications, hsa-miR-769-3p was found to be significantly correlated with the presence of significant coronary atherosclerosis. CONCLUSIONS: This study utilized a superior high-throughput qRT-PCR based method and found that miRNAs are found to be widely expressed in human blood with differences expressed between cellular and extracellular fractions. Importantly, specific miRNAs from circulating plasma are associated with the presence of significant coronary disease.