New candidate genes for ST-elevation myocardial infarction.

BACKGROUND: Despite extensive research in atherosclerosis, the mechanisms of coronary atherothrombosis in ST-elevation myocardial infarction (STEMI) patients are undetermined. OBJECTIVES: Our aim was to find candidate genes involved in STEMI by analysing leucocyte gene expression in STEMI patients, without the influence of secondary inflammation from innate immunity, which was assumed to be a consequence rather than the cause of coronary atherothrombosis. METHODS: Fifty-one patients were included at coronary angiography because of STEMI. Arterial blood was sampled in the acute phase (P1), at 24-48 h (P2) and at 3 months (P3). Leucocyte RNA was isolated and gene expression analysis was performed by Affymetrix Human Transcriptome Array 2.0. By omission of up- or downregulated genes at P2, secondary changes from innate immunity were excluded. Genes differentially expressed in P1 when compared to the convalescent sample in P3 were determined as genes involved in STEMI. RESULTS: Three genes were upregulated at P1 compared to P3; ABCG1 (P = 5.81 × 10-5 ), RAB20 (P = 3.69 × 10-5 ) and TMEM2 (P = 7.75 × 10-6 ) whilst four were downregulated; ACVR1 (P = 9.01 × 10-5 ), NFATC2IP (P = 8.86 × 10-5 ), SUN1 (P = 3.87 × 10-5 ) and TTC9C (P = 7.18 × 10-6 ). These genes were also highly expressed in carotid atherosclerotic plaques. CONCLUSIONS: We found seven genes involved in STEMI. The study is unique regarding the blood sampling in the acute phase and omission of secondary expressed genes from innate immunity. However, the results need to be replicated by future studies.

Associations between echocardiographic manifestations and bacterial species in patients with infective endocarditis: a cohort study.

BACKGROUND: The diagnosis of infective endocarditis (IE) is based on microbiological analyses and diagnostic imaging of cardiac manifestations. Echocardiography (ECHO) is preferred for visualization of IE-induced cardiac manifestations. We investigated associations between bacterial infections and IE manifestations diagnosed by ECHO. METHODS: In this cohort study, data from patients aged 18 years or above, with definite IE admitted at the Karolinska University Hospital between 2008 and 2017 were obtained from Swedish National Registry of Endocarditis. Bacteria registered as pathogen were primarily selected from positive blood culture and for patients with negative blood culture, bacteria found in culture or PCR from postoperative material was registered as pathogen. Patients with negative results from culture or PCR, and patients who did not undergo ECHO during hospital stay, were excluded. IE manifestations diagnosed by ECHO were obtained from the registry. Chi-squared test and two-sided Fisher's exact test was used for comparisons between categorical variables, and student's t test was used for continuous numerical variables. Multivariable analyses were performed using logistic regression. Secular trend analyses were performed using linear regression. Associations and the strength between the variables were estimated using odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered significant. RESULTS: The most common bacteria were Staphylococcus aureus (n = 239, 49%) and viridans group streptococci (n = 102, 21%). The most common manifestations were vegetation in the mitral (n = 195, 40%), aortic (n = 190, 39%), and tricuspid valves (n = 108, 22%). Associations were seen between aortic valve vegetations and Enterococcus faecalis among patients with native aortic valves, between mitral valve vegetations and streptococci of group B or viridans group, between tricuspid valve vegetations and S. aureus among patients with intravenous drug abuse, and between perivalvular abscesses as well as cardiovascular implantable electronic device (CIED)-associated IE and coagulase negative staphylococci (all P < 0.05). CONCLUSIONS: Associations were found between certain bacterial species and specific ECHO manifestations. Our study contributes to a better understanding of IE manifestations and their underlying bacterial etiology, which pathogens can cause severe infections and might require close follow-up and surgical treatment.

The value of a new cardiac magnetic resonance imaging protocol in Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA) - a case-control study using historical controls from a previous study with similar inclusion criteria.

BACKGROUND: Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is common with a prevalence of 6% of all patients fulfilling the diagnosis of myocardial infarction. MINOCA should be considered a working diagnosis. Cardiac Magnetic Resonance (CMR) imaging has recently been suggested to be of great value to determine the cause behind MINOCA. The objectives of this paper are to describe the rationale behind the second Stockholm Myocardial Infarction with Normal Coronaries (SMINC-2) study and to discuss the protocol for investigation of MINOCA patients in the light of the recently published position paper from the European Society of Cardiology. METHODS: The SMINC-2 study is an open non-randomised study using historical controls for comparison. The primary aim is to prove that MINOCA patients investigated with the latest CMR imaging technique can achieve a diagnosis in 70% of all cases entirely by imaging. By including 150 patients we will have >80% chance to prove that the diagnostic accuracy can be improved by 20 absolute % with a p-value of less than 0.05 when compared with CMR imaging in the SMINC-1 study. Furthermore, in addition to invasive coronary angiography, coronary arteries are evaluated by computed tomography angiography to investigate coronary causes and questionnaires are used to describe Quality-of-Life (QoL). By January 1st 2017, 75 patients have been included. DISCUSSION: Whether CMR imaging can provide a diagnosis to an adequate proportion of MINOCA patients is unknown. Well-defined inclusion and exclusion criteria will be used to compare a MINOCA cohort from the population with an appropriate control group. Positive results are likely to influence future guidelines of the management of MINOCA. Furthermore, the study will give mechanistic insights into MINOCA in particular in patients with "true" myocardial infarction and describe QoL in this vulnerable group of patients. TRIAL REGISTRATION: Clinical Trials NCT02318498 .

Ultrasound measurements of carotid intima-media thickness by two semi-automated analysis systems.

Increased carotid intima-media thickness (cIMT) is associated with an increased risk of cardiac events and stroke. Several semi-automated edge-detection techniques for measuring cIMT are used for research and in clinical practice. Our aim was to compare two currently available semi-automated techniques for the measurement of cIMT. Carotid ultrasound recordings were obtained from 99 subjects (mean age 54·4 ± 8·9 years, range 33-69) without known cardiovascular diseases using a General Electric (GE) Vivid 7 ultrasound scanner, 8-MHz transducer. The far-wall cIMT was evaluated 1-2 cm proximal to the carotid bulb. Three diastolic images (ECG R-wave) from the left and three images from the right common carotid arteries were analysed using GE and Artery Measurement System (AMS) semi-automated softwares. Mean systolic and diastolic blood pressures were 120 ± 13 and 76 ± 8 mmHg, respectively. The cIMTmean (left + right)/2 by GE and cIMTmean (left + right)/2 AMS were highly correlated (r = 0·92, P<0·001). Higher values were measured by GE (0·72 ± 0·12 mm) compared with AMS (0·69 ± 0·12 mm), and this was significant (P<0·001). The coefficients of variation for the intra-observer variability of cIMTmean (left + right)/2 were 1·0% (GE) and 2·2% (AMS). cIMTmean measured by GE's semi-automated edge-detection method correlated well with that measured by AMS. However, there were small but significant systematic differences between the cIMTmean values measured by the two techniques. Thus, the use of only one type of measurement program seems favourable in follow-up studies and when evaluating treatment effects.

Regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects.

BACKGROUND: Cardiovascular disease is associated with multiple risk factors including stiff arteries and large adipocytes. Whether the latter two are interrelated is unknown. We aimed to determine whether arterial stiffness is associated with fat cell size and number in subcutaneous or visceral white adipose tissue (WAT). METHODS: A cross-sectional study of 120 obese subjects scheduled for bariatric surgery in whom WAT mass and distribution was assessed by dual-X-ray absorptiometry. Biopsies from visceral (greater omentum) and subcutaneous (abdominal) WAT were obtained to calculate fat cell volume and number. Arterial stiffness was determined as aortic pulse wave velocity (PWV). RESULTS: Visceral adipocyte volume, but not number, was strongly (P<0.0001) and positively correlated with PWV, explaining 20% of the inter-individual variations in this parameter. This relationship remained significant after correction for clinical confounders. PWV correlated positively (r=0.38, P<0.0001) with visceral (but not subcutaneous) WAT mass. Furthermore, PWV was also positively associated with subcutaneous adipocyte volume (r=0.20, P=0.031) and negatively with fat cell number (r=-0.26, P=0.006). However, the relationships between PWV and visceral WAT mass or subcutaneous fat cell size/number became non-significant when controlling for visceral fat cell volume. In a multiple regression analysis to determine the factors that explain variations in PWV, only visceral fat cell volume, age, pulse rate and diastolic blood pressure entered the model, together explaining 42% of the variation in PWV. CONCLUSIONS: Visceral fat cell volume was the only WAT parameter that constituted an independent and significant, positive regressor for arterial stiffness determined by PWV. Although a causal relationship is not established, visceral fat cell volume may explain the well-known correlation between central fat mass, arterial stiffness and cardiovascular risk, at least in severely/morbidly obese subjects.

Effects of Nordic walking on cardiovascular risk factors in overweight individuals with type 2 diabetes, impaired or normal glucose tolerance.

BACKGROUND: Physical activity remains a valuable prevention for metabolic disease. The effects of Nordic walking on cardiovascular risk factors were determined in overweight individuals with normal or disturbed glucose regulation. METHODS: We included 213 individuals, aged 60 ± 5.3 years and with body mass index (BMI) of 30.2 ± 3.8 kg/m(2); of these, 128 had normal glucose tolerance (NGT), 35 had impaired glucose tolerance (IGT) and 50 had type 2 diabetes mellitus (T2DM). Participants were randomized to unaltered physical activity or to 5 h per week of Nordic walking with poles, for a 4-month period. Dietary habits were unaltered. BMI, waist circumference, blood pressure, glucose tolerance, clinical chemistry, maximal oxygen uptake (peak VO(2)) and self-reported physical activity (questionnaire) were assessed at the time of inclusion and after 4 months. The participants in the exercise-intervention group kept a walking diary. RESULTS: In the NGT exercise group, self-reported physical activity increased markedly, and body weight (-2.0 ± 3.8 kg), BMI (-0.8 ± 1.4 kg/m(2)) and waist circumference (-4.9 ± 4.4 cm) (mean ± SD) decreased. Exercise power output (12.9 ± 9.9 W) and peak VO(2) (2.7 ± 2.8 mL/kg/min) increased in the IGT exercise group. More cardiovascular risk factors were improved after exercise intervention in people with NGT compared with those with IGT or T2DM. Exercise capacity improved significantly in all three groups of participants who reported at least 80% compliance with the scheduled exercise. CONCLUSIONS: Nordic walking improved anthropometric measurements and exercise capacity. However, unsupervised Nordic walking may not provide a sufficient increase in exercise intensity to achieve ultimate health-promoting benefits on the cardiovascular parameters assessed in this study, particularly for those with disturbed glucose regulation.

Community-based gender perspectives of triage and treatment in suspected myocardial infarction.

BACKGROUND: The gender perspectives of the triage of acute coronary syndromes (ACS) in a community are insufficiently explored. METHODS: Patients (n=3224) with symptoms of ACS, in whom ECG was sent by the ambulance crew to a coronary care unit (CCU)/ cath lab, were investigated in the municipality of Göteborg in 2004-2007. Background, triage priority, investigations and treatment were analysed (p-values age adjusted) in relation to gender. Data were compared with three published studies (1995-2002: Surveys 1-3). RESULTS: Women were directly admitted to the CCU significantly less frequently than men (23 versus 35%, p<0.0001). Adjusted for ECG findings, age, symptoms and medical history, odds ratio and 95% confidence limits (for direct admission; men versus women) were 0.61; 0.46-0.82. SURVEY 1: Patients with ACS, aged <80, in CCU at a university hospital (n=1744). Only minor differences between women and men, with regard to investigations and treatment, were found. SURVEY 2: Patients discharged from hospital (dead or alive) with AMI, regardless of type of ward (n=1423). Fewer women than men were admitted to CCU and fewer women underwent coronary angiography (21% versus 40%; p=0.02) and coronary revascularisation (12% versus 27%; p=0.004). SURVEY 3: Patients with symptoms of AMI (n=930) and patients with a confirmed AMI (n=130) from a pre-hospital perspective. Women tended to be given lower priority than men both by the ambulance dispatchers and by the ambulance crew. CONCLUSION: In our practice setting, men are given priority over women in admission to CCU, but no gender differences are seen thereafter.

Effects of Nordic walking on health-related quality of life in overweight individuals with type 2 diabetes mellitus, impaired or normal glucose tolerance.

AIMS: To assess the effects of 4 months of increased physical activity on health-related quality of life in overweight individuals with Type 2 diabetes mellitus, normal or impaired glucose tolerance. METHODS: We included 212 individuals without severe physical or cardiovascular impairments aged 61 (57-64) years, with BMI of 29 (27.5-32) kg/m². Numbers are median (25th-75th percentile). Subjects were stratified based on normal glucose tolerance (n = 128), impaired glucose tolerance (n = 34) or Type 2 diabetes mellitus (n = 50). They were randomized into either a control group (n= 125), who maintained unaltered habitual lifestyle, or an exercise intervention group (n = 87), who were directed to engage in Nordic walking with walking poles, 5 h per week over 4 months. Self-reported physical activity and health-related quality of life was assessed at the time of inclusion and after 4 months. RESULTS: Baseline health-related quality of life of this study cohort was similar to, or better than, an age- and sex-matched Swedish population sample, for 12 of 13 scales. Quality of sleep and BMI were improved for participants with normal glucose tolerance after 4 months of Nordic walking, with little or no musculoskeletal pain as compared with control subjects. No correlation was evident between improved quality of sleep and improved BMI. CONCLUSIONS: Quality of sleep improved in the group with normal glucose tolerance following 4 months of Nordic walking. BMI reduction did not account for this improvement. Nordic walking can be introduced in a primary health care setting as a low-cost mode of exercise that promotes weight loss and improved health satisfaction.

Cardiac function in mild primary hyperparathyroidism and the outcome after parathyroidectomy.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity. The extent of cardiovascular abnormalities in patients with mild-asymptomatic disease is unclear. Using sensitive echocardiographic methods, we compared cardiac structure and function in patients with mild PHPT and in healthy controls, and evaluated the changes after parathyroidectomy (PTX). METHODS: In a prospective case-control design, we studied 51 PHPT patients without any cardiovascular risk factors/diseases and 51 healthy matched controls. Cardiac structure, and systolic and diastolic function were evaluated by echocardiography and Doppler tissue imaging (DTI). Blood pressure (BP) and heart rate were measured. RESULTS: We observed no differences in systolic or diastolic function or in cardiac morphology between the PHPT patients and the age-matched healthy controls. The regional peak systolic myocardial velocities (S') measured with DTI decreased at all sites (P<0.05) after PTX (tricuspid annulus 14.23+/-1.85 to 13.48+/-1.79, septal 8.48+/-0.96 to 7.97+/-0.85, and lateral 9.61+/-2.05 to 8.87+/-1.63 cm/s, part of the mitral annulus). At baseline, systolic BP was higher in patients compared to controls (127.6+/-17.1 vs 119.6+/-12.6 mmHg, P<0.05). After PTX, both systolic (127.6+/-17.1 vs 124.6+/-16.6 mmHg, P<0.05) and diastolic (80.3+/-9.6 vs 78.4+/-8.6 mmHg, P<0.05) BP decreased. CONCLUSIONS: Our results indicate that patients with PHPT without cardiovascular risk factors have a normal global systolic and diastolic function and cardiac morphology. BP and the systolic velocities were marginally reduced after PTX, but reflected the values of the control group. Our findings warrant further investigation of the clinical and prognostic significance of these possibly disease-related inotropic effects.

Retrograde blood flow in the aortic arch determined by transesophageal Doppler ultrasound.

BACKGROUND: Aortic arch atheromas may be important sources of cerebral embolism. Aortic plaques are frequently found somewhat distal to the origin of the cerebral arteries, implying that cerebral embolization from such plaques depends on local retrograde blood flow components in this area. Therefore, we investigated the occurrence of blood flow reversal in this part of the aorta. Furthermore, since the presence and magnitude of retrograde flow might be influenced by aortic wall properties, we also studied the relationship between plaque size and distribution, aortic strain and degree of retrograde flow. METHODS: We evaluated aortic arch ante- and retrograde blood flow velocities in 56 patients by transesophageal echocardiography using color-Doppler-guided pulsed-Doppler techniques. The velocity-time integrals (VTI) were measured and the diastolic/systolic VTI ratio was calculated. RESULTS: Retrograde diastolic blood flow was noted in all subjects, and diastolic/systolic VTI ratios were higher (p < 0.05) in patients with plaque >or=4 mm (n = 17) compared to those (n = 39) without. Patients exhibiting plaques exclusively in the aortic arch showed the highest VTI ratios (p < 0.01) and tended to have the lowest strain values. Aortic strain was also reduced in patients >50 years of age (p < 0.01). CONCLUSIONS: Our findings demonstrate retrograde aortic flow in all subjects and its proportion increases in subjects with atherosclerosis, particularly in the aortic arch. Aortic plaques situated distally to the origin of the cerebral arteries are therefore possible sources of cerebral emboli.

Prevalence of micro-emboli in symptomatic high grade carotid artery disease: a transcranial Doppler study.

BACKGROUND AND PURPOSE: Echolucent carotid plaques, as well as downstream micro-embolisation, may be associated with an increased risk of stroke. However, the relationship between carotid plaque ultrasound characteristics and micro-embolic signals (MES) detected in the middle cerebral artery (MCA) is still controversial. The purpose of this study was to investigate the prevalence of MES in patients with symptomatic high-grade internal carotid artery (ICA) stenosis and to identify predisposing factors, such as plaque echogenicity and intra stenotic blood flow velocity pattern. METHODS: 197 patients (mean age 69.5+/-8.6, 161 males) with confirmed symptomatic high-grade ICA stenosis and anti-platelet treatment underwent bilateral MES monitoring for 30 minutes within the anterior circulation, using Power M-mode transcranial Doppler techniques (TCD). Carotid artery plaques were characterized by Gray-Weale scaling. RESULTS: In 32.0% of the patients, we detected MES by TCD within the MCA on the symptomatic side, but the same finding was made in only 4.5% on the corresponding asymptomatic site (p<0.0001). The presence or absence of MES was associated with neither ultrasonic plaque characteristics nor the intrastenotic blood flow velocities at peak systole and end diastole. The median time since the last ischemic event symptoms was shorter in the patient group with MES [+] than in MES [-] (p=0.013). CONCLUSIONS: Despite optimum standard anti-platelet therapy, cerebral micro-embolisation occurs in 30% of patients with symptomatic carotid artery disease, which might therefore be a possible risk factor for recurrent neurological symptoms. However, the presence of MES is independent of intrastenotic blood flow disturbances and grey scale ultrasound plaque characteristics. The presence of MES as an indicator of unstable plaque and thereby a possible risk factor for stroke should be evaluated prospectively using various algorithms for plaque classifications.

Increased arterial stiffness and indication of endothelial dysfunction in long-standing rheumatoid arthritis.

OBJECTIVE: Atherosclerotic progression is accelerated in rheumatoid arthritis (RA). We evaluated arterial stiffness and endothelial dysfunction in RA patients and controls by pulse wave analysis (PWA). METHODS: Thirty RA patients with long-standing disease and 30 age- and sex-matched controls were examined using applanation tonometry of the radial artery before and after vasodilation by terbutaline (endothelium dependent) and nitroglycerin (endothelium independent). The aortic augmentation index (AIx) and time to reflected wave (transit time, Tr) were measured. Using the peripheral pulse curve, the stiffness index (SI) and the reflectance index (RI) were calculated. Tr and SI predominantly reflect large artery stiffness, whereas Aix and RI also reflect small vessel resistance. The PWA measurements were assessed in relation to adhesion molecules [soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intracellular adhesion molecule-1 (sICAM-1)], selectins (E, L and P), and inflammation [erythrocyte sedimentation rate (ESR), haptoglobin, interleukin (IL)-6, IL-1 receptor antagonist (IL-1-Ra), IL-2-soluble receptor (IL-2sR), and tumour necrosis factor receptors-I and -II (TNFR-I and TNFR-II)]. RESULTS: RA patients had shorter Tr (p<0.05) and higher SI (p<0.001) than controls, indicating impaired large vessel compliance. After terbutaline, Tr remained shorter (p<0.05), while SI (p<0.01) and AIx (p<0.01) were higher. The post-terbutaline changes in AIx and RI (DeltaAIx, DeltaRI), suggested to be the best PWA measurements of endothelial function, were smaller in RA patients (p = 0.06). In RA, L-selectin and sVCAM-1 correlated with DeltaRI and L-selectin also with DeltaAIx. Both RI and AIx correlated at baseline with a retrospective inflammatory activity score. CONCLUSION: Arterial stiffness was increased in RA patients. Endothelial dysfunction was implicated and correlated with levels of soluble adhesion molecules. Small vessel resistance correlated with the long-standing inflammatory load in RA.

C-reactive protein, interleukin-6, secretory phospholipase A2 group IIA and intercellular adhesion molecule-1 in the prediction of late outcome events after acute coronary syndromes.

OBJECTIVE: We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS). DESIGN: Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. SETTING: Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Patients with ACS alive at day 30; median follow-up 75 months. RESULTS: Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL-6 and ICAM-1, but not sPLA(2)-IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1-1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1-1.9, P = 0.006). For IL-6, HR was 1.3 for mortality (95% CI: 1.1-1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1-1.8, P = 0.02). For ICAM-1, HR was 1.2 for mortality (95% CI: 1.0-1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0-1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. CONCLUSIONS: In patients with ACS, CRP, IL-6, sPLA(2)-IIA and ICAM-1 are associated with long-term mortality and CHF, but not reinfarction. CRP, IL-6 and ICAM-1 provide prognostic information beyond that obtained by clinical variables.

Admission glycaemia and outcome after acute coronary syndrome.

BACKGROUND: Acute phase hyperglycaemia has been associated with increased mortality in patients with acute coronary syndrome. We investigated whether the predictive value of admission hyperglycaemia for mortality differs between diabetics and non-diabetics with acute coronary syndrome. METHODS: Patients with acute coronary syndrome (n=1957) were followed up prospectively for 45 months. Patients were stratified into quartile groups defined by admission plasma glucose and hyperglycaemia was defined as plasma glucose of >9.4 mmol/l, which was the cut-off value for the 4th quartile. The relationship between admission hyperglycaemia and short-term (< or =30 day) and late (>30 day) mortality was analysed. RESULTS: Of 1957 patients, 22% had a history of diabetes. Among patients without diabetes, those with hyperglycaemia had both a higher 30-day mortality rate (20.2% vs. 3.5%, p<0.0001) and late mortality rate (19.1% vs. 11.7%, p=0.007). Hyperglycaemic patients with diabetes had a higher late mortality rate than diabetic patients with plasma glucose of < or =9.4 mmol/l (29.3% vs. 14.9%, p=0.001). Of patients with hyperglycaemia at admission, those without diabetes had a higher 30-day mortality rate compared with those with diabetes (p=0.002). CONCLUSION: Admission hyperglycaemia is a strong risk factor for mortality in patients with acute coronary syndrome and may be even stronger than a previous history of diabetes. Hyperglycaemic patients without recognised diabetes have a higher short-term mortality risk than hyperglycaemic patients with known diabetes.

Association between glycometabolic status in the acute phase and 21/2 years after an acute coronary syndrome.

OBJECTIVES: To evaluate the association between glycometabolic status in the acute phase and 21/2 years later in patients with acute coronary syndrome (ACS). METHODS: Non-diabetic patients (n = 762) presenting with ACS were prospectively followed up for 21/2 years. Patients were stratified by admission plasma glucose (<6.1 mmol/l, 6.1 - 6.9 mmol/l and >or=7.0 mmol/l) and HbA1c (or=5.5%). The predictive value of glucose levels >or= 7.0 mmol/l and HbA1c >or= 5.5% for glycometabolic disturbance (i.e. diabetes or impaired fasting glycaemia (IFG)) was analysed. RESULTS: Of 762 patients, 13% had a diagnosis of diabetes and 16% had IFG at follow-up. The prevalence of glycometabolic disturbance at follow-up increased with increasing plasma glucose at admission, from 19% in patients with < 6.1 mmol/l to 42% in patients with >or= 7.0 mmol/l. Sixty-one percent of patients with HbA1c >or= 5.5% had glycometabolic disturbance after 21/2 years compared to only 25% of those with HbA1c < 5.5%. CONCLUSION: Non-diabetic patients with ACS and hyperglycaemia are at high risk for developing glycometabolic disturbance. HbA1c may be an even stronger predictor of glycometabolic disturbance than plasma glucose.

Growth hormone alone or combined with metoprolol preserves cardiac function after myocardial infarction in rats.

BACKGROUND AND OBJECTIVE: Beta-adrenoreceptor blocking agents are important for the treatment of myocardial infarction (MI). Accumulating evidence also indicates that growth hormone (GH) improves cardiac function after MI in rats. We aimed to investigate the cardiovascular effects of combined treatment in an animal model of MI. METHODS: MI was induced in rats by ligation of the left coronary artery. Three days after MI, animals were randomly assigned to one of four groups: controls (C) (n=19); GH (n=19) receiving s.c. 2 mg/kg per day rhGH; metoprolol (M) group (n=19) receiving 24 mg/kg per day and combined group (GHM) (n=20) treated with both GH (2 mg/kg per day s.c.) and M (24 mg/kg per day) for 9 days. Transthoracic echocardiography was performed before and after treatment. RESULTS: Serum levels of insulin-like growth factor I were significantly elevated in the GH-group but not in the GHM group compared to controls. Left ventricular volumes, cardiac index, systolic blood pressure, were similar in all groups. Percent changes in ejection fraction compared to baseline were; GH (6.1+/-5.0%) and GHM (6.1+/-4.2%) vs. C (-12.5+/-3.0%), P<0.01, M (-7.3+/-4.2%). The occurrence of aneurysms was not significantly different between the various treatment regimes. CONCLUSION: Treatment with growth hormone alone or in combination with metoprolol preserved left ventricular function after MI.

Similar cardiovascular effects of growth hormone and insulin-like growth factor-I in rats after experimental myocardial infarction.

Accumulating data show that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have major effects on the cardiovascular system. In the present study we have directly compared GH and IGF-I in an in vivo rat model of experimental myocardial infarction. Four weeks after ligation of the left coronary artery, male rats were treated with recombinant human (rh) GH 1.1 mg/kg per day, rhIGF-I 3.0 mg/kg per day or saline s.c. for 2 weeks. Transthoracic echocardiography was performed before and after the treatment period. Both GH and IGF-I reduced total peripheral resistance (P< 0.01), end-systolic wall stress (P< 0.01) and end-systolic short-axis area (P< 0.001 and P< 0.05). GH also increased area fractional shortening (P< 0.05). Stroke volume (SV) and SV index were improved by IGF-I (P< 0.0001), and SV tended to be increased by GH (P= 0.12). In conclusion, GH and IGF-I had similar beneficial effects on systolic function and peripheral resistance after experimental myocardial infarction.

Blood pressure, cardiac structure and severity of obstructive sleep apnea in a sleep clinic population.

OBJECTIVES: We investigated whether the severity of obstructive sleep apnea (OSA) predicts blood pressure or cardiac left ventricular thickness in a clinical population of OSA patients, if adjustments are made for age, gender, use of antihypertensive agents, smoking, body mass index, history of coronary artery disease, hypercholesterolemia and circulating C-peptide concentrations. DESIGN: Relationships in this cross-sectional study were investigated with correlation analysis and multiple regression procedures. PATIENTS AND METHODS: Apnea-hypopnea index (AHI, polysomnography) and office systolic and diastolic blood pressures (SBP and DBP) were measured in 81 subjects referred to a university hospital sleep laboratory. Ambulatory blood pressures were recorded during one 24 h cycle. Left ventricular (LV) muscle size was quantified as two-dimensionally directed M-mode-derived end-diastolic thickness of interventricular septum and posterior chamber wall. RESULTS: After adjustment for separate or the entire set of covariates, AHI predicted office SBP and DBP as well as daytime ambulatory DBP and night-time ambulatory SBP and DBP, but not daytime ambulatory SBP. In contrast, associations between AHI and LV muscle thickness reflected complex inter-relationships with confounding variables. Smoking and age suppressed, whereas body mass index (BMI) and hypertension inflated the relationship between OSA severity and LV muscle thickness in this study. CONCLUSIONS: AHI is an independent predictor of several measures of blood pressure. OSA severity and LV muscle thickness appear to be primarily linked via increased blood pressure.

Assessment of effective orifice area of prosthetic aortic valves with Doppler echocardiography: an in vivo and in vitro study.

OBJECTIVES: We sought to evaluate the Doppler assessment of effective orifice area in aortic prosthetic valves. The effective orifice area is a less flow-dependent parameter than Doppler gradients that is used to assess prosthetic valve function. However, in vivo reference values show a pronounced spread of effective orifice area and smaller orifices than expected compared with the geometric area. METHODS: Using Doppler echocardiography, we studied patients who received a bileaflet St Jude Medical valve (n = 75; St Jude Medical, Inc, St Paul, Minn) or a tilting disc Omnicarbon valve (n = 46; MedicalCV, Incorporated, Inver Grove Heights, Minn). The prosthetic valves were also investigated in vitro in a steady-flow model with Doppler and catheter measurements in the different orifices. The effective orifice area was calculated according to the continuity equation. RESULTS: In vivo, there was a wide distribution with the coefficient of variation (SD/mean x 100%) for different valve sizes ranging from 21% to 39% in the St Jude Medical valve and from 25% to 33% in the Omnicarbon valve. The differences between geometric orifice area and effective orifice area in vitro were 1.26 +/- 0.41 cm(2) for St Jude Medical and 1.17 +/- 0.38 cm(2) for Omnicarbon valves. The overall effective orifice areas and peak catheter gradients were similar: 1.35 +/- 0.37 cm(2) and 25.9 +/- 16.1 mm Hg for St Jude Medical and 1.46 +/- 0.49 cm(2) and 24.6 +/- 17.7 mm Hg for Omnicarbon. However, in St Jude Medical valves, more pressure was recovered downstream, 11.6 +/- 6.3 mm Hg versus 3.4 +/- 1.6 mm Hg in Omnicarbon valves (P =.0001). CONCLUSIONS: In the patients, we found a pronounced spread of effective orifice areas, which can be explained by measurement errors or true biologic variations. The in vitro effective orifice area was small compared with the geometric orifice area, and we suspect that nonuniformity in the spatial velocity profile causes underestimation. The St Jude Medical and Omnicarbon valves showed similar peak catheter gradients and effective orifice areas in vitro, but more pressure was recovered in the St Jude Medical valve. The effective orifice area can therefore be misleading in the assessment of prosthetic valve performance when bileaflet and tilting disc valves are compared.

Investigation of tyrosine nitration in proteins by mass spectrometry.

In vivo nitration of tyrosine residues is a post-translational modification mediated by peroxynitrite that may be involved in a number of diseases. The aim of this study was to evaluate possibilities for site-specific detection of tyrosine nitration by mass spectrometry. Angiotensin II and bovine serum albumin (BSA) nitrated with tetranitromethane (TNM) were used as model compounds. Three strategies were investigated: (i) analysis of single peptides and protein digests by matrix-assisted laser desorption/ionization (MALDI) peptide mass mapping, (ii) peptide mass mapping by electrospray ionization (ESI) mass spectrometry and (iii) screening for nitration by selective detection of the immonium ion of nitrotyrosine by precursor ion scanning with subsequent sequencing of the modified peptides. The MALDI time-of-flight mass spectrum of nitrated angiotensin II showed an unexpected prompt fragmentation involving the nitro group, in contrast to ESI-MS, where no fragmentation of nitrated angiotensin II was observed. The ESI mass spectra showed that mono- and dinitrated angiotensin II were obtained after treatment with TNM. ESI-MS/MS revealed that the mononitrated angiotensin II was nitrated on the side-chain of tyrosine. The dinitrated angiotensin II contained two nitro groups on the tyrosine residue. Nitration of BSA was confirmed by Western blotting with an antibody against nitrotyrosine and the sites for nitration were investigated by peptide mass mapping after in-gel digestion. Direct mass mapping by ESI revealed that two peptides were nitrated. Precursor ion scanning for the immonium ion for nitrotyrosine revealed two additional partially nitrated peptides. Based on the studies with the two model compounds, we suggest that the investigation of in vivo nitration of tyrosine and identification of nitrated peptides might be performed by precursor ion scanning for the specific immonium ion at m/z 181.06 combined with ESI-MS/MS for identification of the specific nitration sites.