Coronary artery calcium and intima-media thickness are associated with level of cytomegalovirus immunoglobulin G in HIV-infected patients.

Coinfection with cytomegalovirus (CMV) may be involved in cardiovascular disease in HIV-infected patients. We found that higher level of CMV immunoglobulin G (IgG) was independently associated with an increased risk of coronary artery calcium and higher intima-media thickness in HIV-infected patients but not in healthy controls after adjustment for other cardiovascular risk factors and levels of herpes viridae IgG.

Association between smoking status assessed with plasma-cotinine and inflammatory and endothelial biomarkers in HIV-positive and HIV-negative individuals.

OBJECTIVES: Smoking is a major contributor to mortality and morbidity in HIV-positive individuals. Our primary objective was to evaluate the association between smoking status determined by plasma cotinine (P-cotinine) concentration and inflammatory and endothelial biomarkers in HIV-positive versus HIV-negative individuals. METHODS: We studied eight inflammatory/endothelial biomarkers [high-sensitivity C-reactive protein (hsCRP), E-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP-9), myeloperoxidase (MPO), tissue type plasminogen activator inhibitor 1 (tPAI) and endothelin] in 105 HIV-positive individuals and 105 HIV-negative individuals matched on age, sex and self-reported smoking status. Smoking status was determined using P-cotinine (a concentration > 14 ng/mL was defined as demonstrating exposure to smoke). We used linear regression models to (1) examine the association between smoking status and inflammatory/endothelial biomarkers in HIV-positive compared with HIV-negative individuals, and (2) to determine whether there was evidence to suggest that the impact of smoking status on the biomarkers differed between HIV-positive and HIV-negative individuals. RESULTS: Of the eight biomarkers, smokers had increased hsCRP, sICAM-1 and MMP-9 concentrations irrespective of HIV status and increasing P-cotinine concentration was associated with increasing hsCRP concentration. We found no interaction between smoking and HIV status. HIV infection was associated with increased hsCRP, E-selectin, sVCAM-1, sICAM-1 and MMP-9 concentrations. Self-reported smoking status differed substantially from smoking status assessed with P-cotinine. CONCLUSIONS: Several biomarkers were associated with smoking status and HIV status. However, our data do not indicate that the effects of smoking on the biomarkers differ between HIV-positive and HIV-negative individuals.

Prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction and non-significant coronary artery disease.

BACKGROUND AND PURPOSE: We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD). METHODS: From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter <50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T >50ng/l or creatine kinase MB >4µg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion). RESULTS: Of the 871 patients admitted with suspected STEMI, 11% (n=95) had non-significant CAD. Of these, 67% (n=64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n=31) of patients, cardiac biomarkers were normal and ECG changes remained stationary. CONCLUSIONS: Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD.

Hypertension and renovascular disease: follow-up on 100 renal vein renin samplings.

The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in the treatment of renovascular hypertension was evaluated. One hundred consecutive patients were included over a 4-year period of time. About half of the patients (49%) were treated interventionally by PTRA (21%), nephrectomy (20%), or vascular surgery (8%). Seven patients (15%) were cured and 15 (32%) had improved (reduction in antihypertensive medicine) after 6 months follow-up, whereas three patients (6%) were cured and 12 (26%) improved after 3-4 years follow-up. Thus, the number of patients cured or improved is comparable with the results from our department reported 20 years ago. However, in the present report, more than twice as many patients were enrolled, leading to double costs. Different indices of lateralisation of the renin generation were calculated for the use in cases of a shrunken kidney (functional share < or =15%). None of the indices clearly discriminated between the patients who did benefit from intervention, and those who did not. The only positive finding was that a peripheral renin concentration lower than 8 mlU/l predicted no effect of intervention, which might lead to the exclusion of 11% of the patients before entering the diagnostic programme. We conclude that the RVRS demands a very restrictive referral pattern if it should be of prognostic value for the blood pressure outcome after intervention. No indices of lateralised renin concentrations proved high predictive value. However, a peripheral renin concentration low in the normal range seems useful as an indicator of no benefit from intervention.

CGRP receptors mediating CGRP-, adrenomedullin- and amylin-induced relaxation in porcine coronary arteries. Characterization with 'Compound 1' (WO98/11128), a non-peptide antagonist.

1. Calcitonin gene-related peptide (CGRP), amylin and adrenomedullin (AM) belong to the same family of peptides. Accumulating evidence indicate that the calcitonin (CT) receptor, the CT receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMPs) form the basis of all the receptors in this family of peptides. 2. Using reverse transcriptase - polymerase chain reaction the presence of mRNA sequences encoding the CRLR, RAMP1 and RAMP2 were demonstrated in porcine left anterior descending (LAD) coronary arteries, whereas porcine calcitonin (CT) receptor mRNA was not present. The partial porcine mRNA sequences shared 82 - 92% nucleotide identity with human sequences. 3. The human peptides alphaCGRP, betaCGRP, AM and amylin induced relaxation with pEC(50) values of 8.1, 8.1, 6.7 and 6.1 M respectively. 4. The antagonistic properties of a novel non-peptide CGRP antagonist 'Compound 1' (WO98/11128), betaCGRP(8 - 37) and the proposed AM receptor antagonist AM(22 - 52) were compared to the well-known CGRP(1) receptor antagonist alphaCGRP(8 - 37). 5. The alphaCGRP(8 - 37) and betaCGRP(8 - 37) induced concentration-dependent (10(-7) - 10(-5) M) rightward shift of both the alphaCGRP and betaCGRP concentration-response curves. betaCGRP(8 - 37) (10(-6) M) had the same effect as alphaCGRP(8 - 37) (10(-6) M), but with less potent rightward shift of the concentration-response curves for alphaCGRP, AM and amylin. 6. Preincubation with 'Compound 1' (10(-7) - 10(-5) M) and AM(22 - 52) (10(-6) M) had no significant antagonistic effect. 7. In conclusion, the building blocks forming CGRP and AM receptors were present in the porcine LAD, whereas those of the amylin receptor were not. alphaCGRP, betaCGRP, AM and amylin mediated vasorelaxation via the CGRP receptors. No functional response was detected to adrenomedullin via the adrenomedullin receptor.

[Early repolarization. Differential diagnosis of electrocardiographic ST segment elevation]. / Tidlig repolarisering. Differentialdiagnostiske overvejelser ved elektrokardiografisk ST-segment-elevation.

'Early repolarisation' (ER) represents a normal electrocardiographic variant with persistent ST segment elevation and is considered a benign condition. ER is found in approximately 1-2% of the population and thus it is common among patients in emergency rooms and coronary care units. ER is not associated with increased mortality or morbidity. The electrocardiographic characteristics of ER include widespread ST segment elevation, upward concavity of the initial portion of the ST segment, notching of the terminal QRS complex, and concordant T waves of large amplitude. The most important differential diagnoses to ER are pericarditis and acute myocardial infarction, AMI. Only through a systematic evaluation in the acute setting are patients with AMI assured the relevant revascularisation therapy. Furthermore patients with ER and without cardiac disease can avoid unnecessary and potentially harmful procedures such as fibrinolysis and coronary angiography.

[Early repolarization. ST-segment elevation as a normal electrocardiographic variant]. / Tidlig repolarisering. ST-segment-elevation som elektrokardiografisk normalvariant.

'Early repolarisation' (ER) represents a normal electrocardiographic variant with persistent ST segment elevation and is considered a benign condition. ER is found in approximately 1% of the population and in up to 13% of patients presenting with chest pain in the emergency room. This case report presents a 49 year-old man with ER suspected of acute myocardial infarction due to the combination of chest pain and electrocardiographic ST segment elevation. [figure: see text] The case report describes the electrocardiographic characteristics associated with the syndrome ER and the problems in distinguishing ER from other ST segment elevation syndromes.

Positive inotropy mediated via CGRP receptors in isolated human myocardial trabeculae.

Isometric contractile force were studied on isolated human myocardial trabeculae that were paced at 1.0 Hz in tissue baths. Alpha calcitonin gene-related peptide (alpha-CGRP) had a potent positive inotropic effect in most trabeculae from both the right atrium and left ventricle, and this effect was partially antagonized by the CGRP(1) receptor antagonist alpha-CGRP-(8-37) (10(-6) M). Amylin and the CGRP(2) receptor agonist [Cys(acetylmethoxy)(2, 7)]CGRP had a positive inotropic effect in some trabeculae, whereas adrenomedullin had no inotropic effect. Using reverse transcriptase-polymerase chain reaction (PCR) mRNAs encoding the human calcitonin receptor-like receptor and the receptor associated modifying proteins (RAMPs) RAMP1, RAMP2, and RAMP3 were detected in human myocardial trabeculae from both the right atrium and left ventricle. In conclusion, functional CGRP(1) and CGRP(2) receptors may mediate a positive inotropic effect at both the atrial and ventricular level of the human heart. mRNAs for calcitonin receptor-like receptor and specific RAMPs further support the presence of CGRP receptors.

Differences between local investigator and core laboratory interpretation of the admission electrocardiogram in patients with unstable angina pectoris or non-Q-wave myocardial infarction (a Thrombin Inhibition in Myocardial Ischemia [TRIM] substudy).

The present study compares the on-site interpretation of an admission electrocardiogram (ECG) with core laboratory results in a large, multicenter trial of 516 patients diagnosed with unstable angina pectoris or non-Q-wave myocardial infarction. The local investigators evaluated the admission ECG regarding ST-T changes before the ECGs were sent to the core laboratory for blinded interpretation. The strength of agreement between the observations was described by kappa statistics. There was a poor agreement regarding identification of ST-segment elevation, with 17 patients identified by the local investigator versus 92 by the core laboratory (kappa = 0.05). There was a fair agreement on ST-segment depression with 158 patients diagnosed on-site versus 64 by the core laboratory (kappa = 0.38). Identification of T-wave inversion demonstrated good agreement with 306 patients diagnosed on-site versus 280 by the core laboratory (kappa = 0.63). A moderate agreement regarding identification of a normal ECG was found with 101 patients on-site versus 135 in the core laboratory (kappa = 0.42). Independent variables, including peak creatine kinase-MB and 30-day outcome, were more closely related to core laboratory results than the local investigator's interpretation of the admission ECG. Thus, in the present study, considerable differences were demonstrated between the on-site interpretation of the admission ECG and the blinded evaluation performed in the core laboratory regarding relatively simple electrocardiographic variables. The results suggest that more widespread use of independent evaluation of clinical data should be incorporated in future clinical trials.

Role of the adrenal medulla in control of blood pressure and renal function during frusemide-induced volume depletion.

OBJECTIVE: To examine the role of the adrenal medulla in reflex control of mean arterial pressure (MAP), heart rate and renal function parameters during frusemide-induced volume depletion. DESIGN: Frusemide (6 mg/kg per h) was administered intravenously to two groups of chronically instrumented rats with either sham adrenal medullectomy (n = 15) or adrenal medullectomy (n = 11). RESULTS: Adrenal medullectomy reduced adrenal adrenaline concentration by 99% and plasma adrenaline concentration by 97%. Plasma corticosterone levels were similar in the two groups, which suggests that adrenal cortical function was not affected by adrenal medullectomy. Although frusemide did not affect arterial pressure in the sham-operated rats, MAP fell by 21 +/- 3 mmHg (mean +/- SEM) during frusemide diuresis in the rats with adrenal medullectomy. Heart rate was lower in the rats with adrenal medullectomy than in the sham-operated rats throughout the study. There were no major differences in renal haemodynamics or overall renal water and sodium handling between the two groups but, at the time of maximal activation of compensatory sodium reabsorption, fractional sodium excretion in the distal nephron segment was significantly higher in the rats with adrenal medullectomy than in the sham-operated rats. CONCLUSIONS: Adrenal medullary adrenaline release is essential in the control of MAP during frusemide-induced volume depletion. Circulating adrenaline might contribute, by modifying distal tubular sodium reabsorption, to compensatory sodium reabsorption during frusemide-induced volume depletion.