Elevated serum free light chains predict cardiovascular events in type 2 diabetes

OBJECTIVE: Elevated polyclonal serum immunoglobulin free light chains (FLCs; combined FLCκ+FLCλ [cFLC]) are associated with adverse clinical outcomes and increased mortality; we investigated cFLC and cardiovascular disease (CVD) events in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 352 south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C-reactive protein (hsCRP), and standard biochemistry were measured. CVD events over 2 years were recorded and assessed usingmultiple logistic regression. RESULTS: cFLC levels were elevated significantly in 29 of 352 (8%) patients with CVD events during 2 years of follow-up (50.7 vs. 42.8mg/L; P = 0.004). Inmultivariate analysis, elevated cFLC (>57.2 mg/L) was associated with CVD outcomes (odds ratio 3.3 [95% CI 1.3-8.2]; P = 0.012) and remained significant after adjusting for age, albumin-to-creatinine ratio, diabetes duration, or treatment. CONCLUSIONS: cFLC elevation is a novel marker for CVD outcomes in type 2 diabetes that warrants further investigation. © 2014 by the American Diabetes Association.

Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia

Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient's evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting. © 2014 American Heart Association, Inc.

Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses

Objective - The purpose of this study was to assess cardiac function and cell damage in intrauterine growth-restricted (IUGR) fetuses across clinical Doppler stages of deterioration. Study Design - One hundred twenty appropriate-for-gestational-age and 81 IUGR fetuses were classified in stages 1/2/3 according umbilical artery present/absent/reversed end-diastolic blood flow, respectively. Cardiac function was assessed by modified-myocardial performance index, early-to-late diastolic filling ratios, cardiac output, and cord blood B-type natriuretic peptide; myocardial cell damage was assessed by heart fatty acid–binding protein, troponin-I, and high-sensitivity C-reactive protein. Results - Modified-myocardial performance index, blood B-type natriuretic peptide, and early-to-late diastolic filling ratios were increased in a stage-dependent manner in IUGR fetuses, compared with appropriate-for-gestational-age fetuses. Heart fatty acid–binding protein levels were higher in IUGR fetuses at stage 3, compared with control fetuses. Cardiac output, troponin-I, and high-sensitivity C-reactive protein did not increase in IUGR fetuses at any stage. Conclusion - IUGR fetuses showed signs of cardiac dysfunction from early stages. Cardiac dysfunction deteriorates further with the progression of fetal compromise, together with the appearance of biochemical signs of cell damage.

Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision

The diagnosis of prosthetic joint infection and its differentiation from aseptic loosening remains problematic. The definitive laboratory diagnostic test is the recovery of identical infectious agents from multiple intraoperative tissue samples; however, interpretation of positive cultures is often complex as infection is frequently associated with low numbers of commensal microorganisms, in particular the coagulase-negative staphylococci (CNS). In this investigation, the value of serum procalcitonin (PCT), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) as predictors of infection in revision hip replacement surgery is assessed. Furthermore, the diagnostic value of serum IgG to short-chain exocellular lipoteichoic acid (sce-LTA) is assessed in patients with infection due to CNS. Presurgical levels of conventional serum markers of infection including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) is also established. Forty-six patients undergoing revision hip surgery were recruited with a presumptive clinical diagnosis of either septic (16 patients) or aseptic loosening (30 patients). The diagnosis was confirmed microbiologically and levels of serum markers were determined. Serum levels of IL-6 and sICAM-1 were significantly raised in patients with septic loosening (P=0.001 and P=0.0002, respectively). Serum IgG to sce-LTA was elevated in three out of four patients with infection due to CNS. In contrast, PCT was not found to be of value in differentiating septic and aseptic loosening. Furthermore, CRP, ESR and WBC were significantly higher (P=0.0001, P=0.0001 and P=0.003, respectively) in patients with septic loosening. Serum levels of IL-6, sICAM-1 and IgG to sce-LTA may provide additional information to facilitate the diagnosis of prosthetic joint infection.

Addition of PLA2 to CRP enhances sepsis diagnosis

Letter to the Editor refers to: Fredrikke Christie Knudtzen, Stig Lønberg Nielsen, Kim Oren Gradel, Annmarie Touborg Lassen, Hans Jørn Kolmos, Thøger Gorm Jensen, Pernille Just Vinholt, Court Pedersen, Characteristics of patients with community-acquired bacteremia who have low levels of C-reactive protein (≤20 mg/L), Journal of Infection, Volume 68, Issue 2, February 2014, Pages 149-155

Risk factors of coronary heart disease and correlates of type 2 diabetes among Cuban Americans

Cuban Americans, a minority Hispanic subgroup, have a high prevalence of type 2 diabetes. Persons with diabetes experience a higher rate of coronary heart disease (CHD) compared to those without diabetes. The objectives of the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) are to investigate the risk factors of CHD and the etiology of diabetes among diabetics of minority ethnic populations. No information is available on the etiology of CHD risks for Cuban Americans. ^ This cross-sectional study compared Cuban Americans with (N = 79) and without (N = 80) type 2 diabetes residing in South Florida. Data on risk factors of CHD and type 2 diabetes were collected using sociodemographics, smoking habit, Rose Angina, Modifiable Activity, and Willet's food frequency questionnaires. Anthropometrics and blood pressure (BP) were recorded. Glucose, glycated hemoglobin, lipid profile, homocysteine, and C-reactive protein were assessed in fasting blood. ^ Diabetics reported a significantly higher rate of angina symptoms than non-diabetics (P = 0.008). After adjusting for age and gender, diabetics had significantly (P < 0.001) larger waist circumference and higher systolic BP than non-diabetics. There was no significant difference in major nutrient intakes between the groups. One quarter of subjects, both diabetics and non-diabetics, exceeded the intake of percent calories from total fat and almost 60% had cholesterol intake >200 mg/d and more than 60% had fiber intake <20 gm/d. The pattern of physical activity did not differ between groups though, it was much below the recommended level. After adjusting for age and gender, diabetics had significantly (P < 0.001) higher levels of blood glucose, glycated hemoglobin, triglycerides, and homocysteine than non-diabetics. In contrast, diabetics had significantly (P < 0.01) lower levels of high-density lipoprotein cholesterol (HDL-C). ^ Multivariate logistic regression analyses showed that increasing age, male gender, large waist circumference, lack of acculturation, and high levels of triglycerides were independent risk factors of type 2 diabetes. In contrast, moderate alcohol consumption conferred protection against diabetes. ^ The study identified several risk factors of CHD and diabetes among Cuban Americans. Health care providers are encouraged to practice ethno-specific preventive measures to lower the burden of CHD and diabetes in Cuban Americans. ^

Cardiovascular risk factors in Turkish immigrants with type 2 diabetes living in the Netherlands

The cross sectional study investigated the association of tobacco smoke, vitamin D status, anthropometric parameters, and kidney function in Turkish immigrants with type 2 diabetes (T2D) living in the Netherlands. Study sample included a total of 110 participants aged 30 years and older (males= 46; females= 64). Serum cotinine, a biomarker for smoke exposure, was measured with a solid-phase competitive chemiluminescent immunoassay. Serum 25-hydroxyvitamin D [25(OH)D] was determined by electrochemiluminescence immunoassay (ECLIA). Measures of obesity including: body weight, body mass index (BMI), waist circumference (WC), and hip circumference (HC) were measured. Waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were calculated. Urine albumin was measured by immunoturbidimetric assay. Urine creatinine was determined using the Jaffe method. All statistical analyses were performed using SPSS, version 19.0 (SPSS Inc., Chicago, IL, USA). Independent samples t-test, chi-squared tests, multiple linear regression and logistic regression analysis were used. Cotinine levels were positively associated with cholesterol to HDL ratio and atherosclerosis-index. Serum 25(OH)D levels were negatively associated with diastolic blood pressure. Gender-specific associations between anthropometric measures and high sensitivity C-reactive protein (hs-CRP) levels were observed. Hs-CRP was positively associated with WC and WHR in males and WHtR in females. Microalbuminuria (MAU), as determined by albumin-to-creatinine ratio, was present in 21% of the Turkish immigrants with T2D. Participants with hypertension were 6.58 times more likely (adjusted odds ratio) to have positive MAU as compared to normotensive participants. Our findings indicate that serum cotinine, 25(OH)D, hs-CRP, and MAU may be assessed as a standard of care for T2D management in the Turkish immigrant population. Further research should be conducted following cohorts to determine the effects of these biomarkers on CVD morbidity and mortality.

Comparison of coronary heart disease risk factors in foreign -born and United States-born Afro Caribbean Americans and African Americans in south Florida

In a cross-sectional study design, risk factors for coronary heart disease (CHD) were evaluated in three groups: 66 Afro Caribbeans (FBCA) living in the US for less than 10 years, 62 US-born Afro Caribbean (USBCA) and 61 African American (AA) adults (18–40 years), with equal numbers of males and females in each group. Socio-demographic, dietary, anthropometric and blood pressure data were collected. Fasting blood glucose, blood lipids and high-sensitivity C-reactive protein (hs-CRP) were determined. ^ The USBCA and AA participants compared to the FBCA participants consumed significantly (p < 0.05) more mean total fat (g) (66.3 ± 41.7 and 73.0 ± 47.8 vs. 52.8 ± 32.3), saturated fat (g) (23.1 ± 14.9 and 24.9 ± 15.8 vs. 18.6 ± 11.5), percent energy from fat (%) (33.1 ± 6.5 and 31.4 ± 6.4 vs. 29.3 ± 6.8), fat servings (1.8 ± 1.2 and 1.5 ± 1.0 vs. 1.2 ± 0.9), dietary cholesterol (mg) (220.4 ± 161.9 and 244.1 ± 155.0 vs. 168.8 ± 114.0) and sodium (mg) (2245.2 ± 1238.3 and 2402.6 ± 1359.3 vs. 1838.0 ± 983.4) and less than 2 servings of fruits per day (%) (86.9 and 94.9 vs. 78.5). These differences were more pronounced in males compared to females and remained after correcting for age. Also, the percentages of USBCA and AA participants who were obese (17.1% and 23.0%, respectively) were significantly (p < 0.05) higher compared to FBCA (7.6%) participants. More USBCA and AA than FBCA individuals smoked cigarettes (4.8% and 6.6% vs. 0.0%) and consumed alcoholic beverages (29.0% and 50.8% vs. 24.2%). The mean hs-CRP level of the AA participants (2.2 ± 2.7 mg/L) was significantly (p < 0.01) higher compared to the FBCA (1.1 ± 1.3 mg/L) and USBCA (1.3 ± 1.6 mg/L) participants. ^ The FBCA participants had a better CHD risk profile than the USBCA and AA participants. Focus should be placed on the ethnic and cultural differences in a population to better understand the variations in health indicators among different ethnic groups of the same race. This focus can provide healthcare professionals and policy planners with the opportunity to develop culturally sensitive programs and strategies for the improvement of health outcomes. ^

HIV infection and drugs of abuse: role of acute phase proteins

Background HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated. Methods Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured. Results Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects. Conclusions These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression.

Serum Adiponectin and Ghrelin, Metabolic Syndrome and Diabetes Status in Cuban Americans

Purpose: Metabolic syndrome (MetS) is associated with the development of cardiovascular disease (CVD) and type 2 diabetes. Decreases in circulating adiponectin and ghrelin have been associated with MetS. Our primary aim was to evaluate the relationship of MetS with adiponectin and ghrelin for Cuban Americans with and without type 2 diabetes. Methods: Cross-sectional study of 367 adults, self identified as Cuban extraction and randomly recruited from a mailing list of Broward and Miami-Dade counties. Fasted whole blood for adiponectin (ADPN) was collected using K3EDTA tubes and measured by ELISA. Ghrelin was assayed with fasted blood plasma by Enzyme Immunometric Assay. MetS and 10-year risk for coronary heart disease (CHD) were determined using the ATP III criteria. Results: Adiponectin (F=51.8, R2 =0.21 p<0.001) and ghrelin (F=12.77, R 2 =0.06, p<0.001) differed by diabetes status (ANOVA) not age and gender. In stepwise linear regression models triglyceride levels ≥ 150 mg/dL negatively corresponded (coefficient = -0.23) with ghrelin levels for persons without diabetes (F=7.45, R2 =0.053, p=0.007); abdominal obesity and fasting plasma glucose predicted high sensitivity C-reactive protein (hs-CRP) for persons with and without diabetes (F=16.3, R2 = 0.144, p <0.001). Conclusion: Low ghrelin levels were associated with MetS regardless of diabetes status. High adiponectin levels were related to a low probability for those without diabetes only. There was a positive association of hs-CRP with BMI, MetS and number of MetS components.

A influência da perda de peso no perfil inflamatório de mulheres com síndrome dos ovários policísticos

The polycystic ovary syndrome (PCOS) is considered the most common endocrine disorder in reproductive age women, with a prevalence ranging from 15 to 20%. In addition to hormonal and reproductive changes, it is common in PCOS the presence of risk factors for developing cardiovascular disease (CVD) and diabetes mellitus, insulin resistance (IR), visceral obesity, chronic low-grade inflammation and dyslipidemia. Due to the high frequency of obesity associated with PCOS, weight loss is considered as the first-line treatment for the syndrome by improving metabolic and normalizes serum androgens, restoring reproductive function of these patients. Objectives: To evaluate the inflammatory markers and IR in women with PCOS and healthy ovulatory with different nutritional status and how these parameters are displayed after weight loss through caloric restriction in with Down syndrome. Methods: Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed in serum samples from 40 women of childbearing age. The volunteers were divided into four groups: Group I (not eutrophic with PCOS, n = 12); Group II (not eutrophic without PCOS, n = 10), Group III (eutrophic with PCOS, n = 08) and Group IV (eutrophic without PCOS, n = 10). The categorization of groups was performed by body mass index (BMI), according to the World Health Organization (WHO) does not eutrophic, overweight and obesity (BMI> 25 kg / m²) and normal weight (BMI <24.9 kg / m²). IR was determined by HOMA-IR index. In the second phase of the study a controlled dietary intervention was performed and inflammatory parameters were evaluated in 21 overweight and obese women with PCOS, before and after weight loss. All patients received a low-calorie diet with reduction of 500 kcal / day of regular consumption with standard concentrations of macronutrients. Results: Phase 1: PCOS patients showed increased levels of CRP (p <0.01) and HOMAIR (p <0.01). When divided by BMI, both not eutrophic group with PCOS (I) as eutrophic with PCOS (III) showed increased levels of CRP (I = 2.35 ± 0,55mg / L and 2.63 ± III = 0,65mg / L; p <0.01) and HOMA-IR (I = 2.16 ± 2.54 and III = 1.07 ± 0.55; p <0.01). There were no differences in TNF-α and IL-6 between groups. Step 2: After the weight loss of 5% of the initial weight was reduced in all of the components of serum assessed inflammatory profile, PCR (154.75 ± 19:33) vs (78.06 ± 8.9) TNF α (10.89 ± 5.09) vs (6:39 ± 1:41) and IL6 (154.75 ± 19:33) vs (78.06 ± 08.09) (p <0:00) in association with improvement some hormonal parameters evaluated. Conclusion: PCOS contributed to the development of chronic inflammation and changes in glucose metabolism by increasing CRP, insulin and HOMA-IR, independent of nutritional status. The weight loss, caloric restriction has improved the inflammatory condition and hormonal status of the evaluated patients.

Receptores de citocinas proinflamatórias na pré-eclâmpsia

Preeclampsia is a disease specific of human pregnancy that affects 3-8% of pregnant women, and it is one of the three leading causes of maternal mortality and morbidity. The disease is characterized by hypertension and proteinuria after the 20th week of gestation. The risk factors for this disease are not completely understood but appear to include dysregulation of the immune response arising from defects in placentation, environmental and genetic factors. This study aimed to determine whether the variation in the amount of proinflammatory cytokine receptors IL-1R2, IL-6R and TNF-αR1 would be involved in preeclampsia. They were recruited women with preeclampsia (n=24) and women who evolved during pregnancy without changes in blood pressure (n=12) were recruited. Clinical and laboratory data were collected. The cytokine receptors (IL-1R2, TNF-αR1 and IL-6R) were assessed in mononuclear cells isolated from peripheral blood using flow cytometry (Control = 8; PE = 24). C-reactive protein (CRP) was determined by CRP ultrasensitive method (Control = 7; PE = 18) was performed using sera pregnant women. Women with preeclampsia had higher weight at the beginning of the pregnancy (p=0.0171) and lower gestational age at delivery (0.0008). Classical monocytes were decreased in preeclampsia but not intermediate or non-classical monocytes. The frequency of IL-1R2 pro inflammatory cytokine receptors is decreased in women with PE only in the subpopulation of non-classical monocytes (p = 0.0011). TNF-αR1 receptor and IL-6R, had a decreased frequency in the three subpopulations of monocyte (classic, intermediate and non-classical) when compared to women with normal pregnancy. An increase in IL-1R2 receptor in TCD4+ lymphocytes, but a decrease in TNF-receptor and IL-6R in women with preeclampsia were found. No differences in the frequency of those receptors in CD3+/CD8+ in preeclampsia. There was no difference in C-reactive protein in preeclampsia. The reduction in the amount of IL-1R2, TNF- αR1 and IL-6R monocytes and lymphocytes can be involved in the regulation of inflammation observed in preeclampsia, contributing to disease.

Determinaçao das principais proteínas de fase aguda e do índice prognóstico inflamatório nutricional (IPIN) em cachorrodo-mato (Cerdocyon thous - Linnaeus, 1766)

The dog-eating fox (Cerdocyon thous - Linnaeus, 1766) is a medium sized canid widely distributed in South America and occurs in almost all of Brazil. Among the main threats to their conservation are the roadkill mainly caused by habitat loss. The shortage of laboratory bush dogs data affect the veterinary medical care hindering the application of appropriate therapies. This study aimed to evaluate the levels of C-reactive protein, albumin, pre-albumin, ceruloplasmin, haptoglobin and Afla 1 acid glycoprotein and the Prognostic Index Inflammatory Nutritional (IPIN) in this species, thus obtaining a first description of these prognostic markers. They collected 1.5 ml of blood by jugular access 8 of Mato Dogs copies (thous thous) from the Laboratory of collection of Teaching and Research in Wildlife (limpets), Faculty of Veterinary Medicine, Federal University of Uberlândia for exams routine. The samples were collected via the jugular vein after physical restraint of animals and trichotomy of the region. After statistical analysis, the values were: albumin: between 2.7 and 3.0 g / dl, alpha 1-acid glycoprotein: between 0.19 and 0.21 g / l, C-reactive protein: between 1.7 and 2 2, prealbumin between 30 and 35 mg / l haptoglobin: between 0.078 and 0.156 and IPIN ≤ 0.006 being considered normal and values ≥ 0.006 considered high. This press description will serve as a basis for studies where animals may be used with specific diseases and, after analysis, compared with the values found in this study and verified the behavior follows the likeness of domestic dogs.

Vitamin D, d-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study

© 2015.To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6. months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 21 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.

Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers

Cardiac Syndrome X (CSX), the presence of angina pectoris with objective signs of myocardial ischaemia despite angiographically normal epicardial coronary arteries, appears to be due to coronary microvascular dysfunction and is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We aimed to further characterise this relationship by prospectively analysing a wide variety of molecular biomarkers in a cohort of CSX patients thereby charting the changes in biomarkers throughout the natural history of CSX from its initial diagnosis to eventual disease quiescence. We found that CSX patients, when compared to healthy controls, have a persistent low-grade systemic inflammatory response characterised by an elevation of Tumour Necrosis Factor and Interferon-gamma, regardless of the presence of contemporaneous signs or symptoms of disease activity. Interleukin-6 and C-reactive Protein (CRP) are only elevated when patients have clinical evidence of disease activity and may be state markers in CSX. Moreover, CRP levels appear to correlate with signals of disease severity such as the time taken to develop symptoms during exercise stress testing. We have also demonstrated that the enzyme Indoleamine-2,3- dioxygenase is upregulated in active disease thus providing a possible explanation for the increased burden of psychological disease encountered in CSX. Analysis of the microRNA transcriptome showed that miR-143 is significantly under-expressed in CSX patients. This could allow phenotype switching in vascular smooth muscle cells with the resultant vascular remodelling causing reduced vessel responsiveness to local rheological stimuli and reduced luminal diameter with consequent increased microvascular resistance during times of increased myocardial oxygen demand, thereby limiting maximal hyperaemia during exercise. Our findings corroborate many previous hypotheses regarding the role of inflammation in CSX, generate new insights into possible pathogenic mechanisms and offer new therapeutic targets for the future management of this important cardiological condition.