Levels of Lipoprotein (a) in patients with coronary artery disease with and without inflammatory rheumatic disease: a cross-sectional study.

OBJECTIVES: Patients with various inflammatory rheumatic diseases (IRDs) have increased risk of atherothrombotic disease. Lipoprotein (a) (Lp(a)) is a risk factor for atherosclerosis but its role in IRD with accompanying coronary artery disease (CAD) is still unclear. We aimed to examine if serum Lp(a) levels differed between CAD patients with and without accompanying IRD. DESIGN: A cross-sectional observational, patient-based cohort study. SETTING: Referred centre for coronary artery bypass grafting in the South Eastern part of Norway. PARTICIPANTS: 67 CAD patients with IRD (CAD/IRD) and 52 CAD patients without IRD (CAD/non-IRD). All patients were Caucasians, aged >18 years, without any clinically significant infection or malignancy. METHODS: Lp(a) levels in serum were analysed by particle enhanced immunoturbidimetric assay, and Lp(a) levels were related to clinical and biochemical characteristics of the patient population. RESULTS: We found no differences in serum levels of Lp(a) between CAD patients with and without IRD. In general, we found that Lp(a) correlated poorly with clinical and biochemical parameters including C reactive protein with the same pattern in the CAD/non-IRD and CAD/IRD groups. CONCLUSIONS: Our data do not support a link between inflammation and Lp(a) levels in CAD and in general Lp(a) levels were not correlated with other risk factors for cardiovascular disease.

Differential expression of vitamin D associated genes in the aorta of coronary artery disease patients with and without rheumatoid arthritis.

BACKGROUND: Vitamin D has an important role in the immune system, and has been linked to rheumatoid arthritis (RA) and coronary artery disease (CAD). The exact mechanisms by which vitamin D is involved in these processes are still unclear. Therefore, we wanted to search for differences in expression of genes involved in the vitamin D receptor (VDR) activation pathway and genes that are known to alter upon vitamin D stimulation, in the aortic adventitia of CAD patients with and without RA. METHODS: Affymetrix microarray was used to determine gene expression profile in surgical specimens from the adventitia of the ascending aorta of CAD patients with RA (n = 8) and without RA (n = 8) from the Feiring Heart Biopsy Study. RESULTS: We identified three vitamin D associated genes that were differentially expressed between RA and non-RA patients: Growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) (FC = 1.47; p = 0.006), Nuclear Receptor Co-repressor 1 (NCOR1) (FC = 1,21; p = 0.005) and paraoxonases 2 (PON2) (FC = -1.37; p = 0.01). High expression of GADD45A in RA tissues was confirmed by real-time qRT-PCR. GADD45A expression correlated with plasma levels of 1,25(OH)2D3 (rs = 0.69; p = 0.003). CONCLUSIONS: Microarray analyses revealed higher expression of GADD45A and NCOR1; and lower expression of PON2 in the aortic adventitia of RA than non-RA patients. Further studies are needed to elucidate if and how GADD45A, NCOR1 and PON2 are involved in the development of accelerated atherosclerosis in RA. In theory, some of these factors might have proatherogenic effects whereas others might reflect an underlying vascular pathology promoting atherogenesis (such as vascular stress).

Gastropericardial fistula presenting with cardiac arrest: a case report.

INTRODUCTION: Gastropericardial fistulas are rare conditions, with less than 100 reported cases. The diagnosis is associated with significant morbidity, prolonged hospitalization and often has a fatal outcome. CASE PRESENTATION: We describe a unique case of cardiac arrest caused by pneumopericardium and cardiac tamponade as the acute presentation of a gastropericardial fistula, in a patient admitted with an infection of unknown origin. Rapid return of spontaneous circulation occurred, and a computed tomography scan revealed the diagnosis. A benign penetrating ulcer was found on gastroscopy, and surgical management with laparotomy and gastrorrhaphy was performed. The patient had no risk factors for gastric ulceration. However, he had significant comorbidity, which makes survival through a complicated postoperative course to full recovery remarkable. DISCUSSION: This case shows that pneumopericardium due to a penetrating benign gastric ulcer can cause cardiac tamponade, and illustrates the value of a multidisciplinary approach to management.

Inflammatory cell infiltrates in the heart of patients with coronary artery disease with and without inflammatory rheumatic disease: a biopsy study.

BACKGROUND: The cause of premature cardiovascular disease (CVD) in inflammatory rheumatic diseases (IRDs) has not been fully elucidated. As inflammation may play a role, we wanted to compare the occurrence and extent of inflammatory cell infiltrates (ICIs), small vessel vasculitis, and the amount of adipose tissue and collagen in cardiac biopsies taken from patients with coronary artery disease with and without IRDs. METHODS: From among the Feiring Heart Biopsy Study subjects, we selected patients undergoing coronary artery bypass grafting from whom paraffin-embedded, formalin-fixed specimens from the right atrium were available. The sample comprised 48 patients with IRD and 40 non-IRD patients. Hematoxylin and eosin staining was used to examine the presence and location of ICIs and vasculitis, and Lendrum (Martius yellow, scarlet, and blue) staining was carried out for collagen and adipose tissue. RESULTS: Epicardial ICIs were found in 27 (56 %) patients with IRD and 24 (60 %) non-IRD patients. There were no significant differences between patients with IRD and non-IRD patients in the amount of cardiac ICIs and adipose tissue, but patients with IRD had more collagen in the myocardium than non-IRD patients. Small vessel vasculitis was not observed in any cardiac specimen. Patients with epicardial ICIs were, on average, 7 years younger than those without. CONCLUSIONS: Our results do not support the notion that inflammation in cardiac peri-, epi-, and myocardium plays a more important role in CVD of patients with IRD than non-IRD patients. The increased amount of collagen in the myocardium of patients with IRD suggests differences in extracellular matrix composition and/or mass, which might play a role in cardiac remodeling, and represent targets for novel therapies against heart failure.

Postoperatively increased serum alanine aminotransferase level is closely associated with mortality after cardiac surgery.

BACKGROUND: Hepatic biomarkers are often not assessed routinely after cardiac surgery. Alanine aminotransferase (ALT) has become the primary biomarker of any type of liver injury. Our purpose was to study the prognostic value of serum ALT in early and late mortality. METHODS: Patients subjected to any type of cardiac operation from January 1999 through December 2010 were studied. According to postoperative maximum ALT level, four groups were created: group 1 = ALT ≤ 50 U/L (n = 8,669), group 2 = ALT 50 to 150 U/L (n = 3,055), group 3 = ALT 151 to 500 U/L (n = 248), and group 4 = ALT > 500 U/L (n = 50). Cox multivariate modeling was used for survival analysis. RESULTS: Patients in groups 3 and 4 had increased 30-day mortality (hazard ratio [HR] = 8.07 [4.15-15.69], p < 0.001 and HR = 19.07 [9.88-36.80], p < 0.001, respectively). Late mortality was increased for group 4 after final adjustments (HR = 1.87 [1.18-2.95], p = 0.007). CONCLUSION: Elevated postoperative ALT level (above 150 U/L) is closely associated with early mortality after cardiac surgery. ALT level above 500 U/L implies a substantial liver dysfunction with a considerable negative association on both early and late survival.

Postcardioplegia ventricular fibrillation: no impact on subsequent survival.

OBJECTIVES: At aortic declamping after cardioplegic cardiac arrest, the initial rhythm can be broadly classified as ventricular fibrillation (VF) or non-VF. VF can be treated with potassium-induced conversion and direct-current countershock is only applied if potassium treatment fails. We aimed to investigate whether there are any differences between these groups of patients in regard to outcomes. DESIGN: From January 1999 through December 2010, 12,113 patients underwent various types of cardiac surgery. Data from every patient were consecutively registered. Survival was established through the Norwegian National Registry. Cox multivariable modeling with adjustment for clinical, biochemical, and medication baseline data was used for survival analysis. RESULTS: The mean follow-up time was 7.4 years and total patient-years were 89,268. The percentage of all-cause deaths was 24.9. Adjusted survival for patients with no postcardioplegia VF (n = 9723) and patients with successful potassium-induced conversion (n = 1877) was completely identical. Four hundred patients with electrical conversion after failed potassium treatment had a nonsignificant trend toward an increased mortality (hazard ratio, 95% confidence interval: 1.19 (0.99-1.4); p = 0.07). CONCLUSIONS: This is the first study reporting the association between postcardioplegia VF, its treatment with potassium and outcome. No impact was found on outcome as judged by all-cause mortality.

Pentraxin 3, a novel cardiovascular biomarker, is expressed in aortic specimens of patients with coronary artery disease with and without rheumatoid arthritis.

BACKGROUND: The aims were to evaluate the presence and extent of pentraxin 3 depositions in specimens from the outer layers of the aorta and from the internal thoracic artery of patients with coronary artery disease with and without rheumatoid arthritis and to search for relationships between pentraxin 3 and vascular inflammation. METHODS: Using histochemistry and immunohistochemistry, we examined biopsies from the aortic adventitia and from the internal thoracic artery (both with adjacent perivascular tissue), removed during coronary artery bypass grafting in 19 rheumatoid arthritis and 20 non-rheumatoid-arthritis patients, for presence/extent of pentraxin 3 depositions, inflammatory cell infiltrates, and fibrosis. RESULTS: In the aorta, pentraxin 3 deposition occurred in all specimens, mostly at sites with inflammatory cell infiltrates or fibrosis, and their extent was related to the extent of inflammatory cell infiltrates (rho=0.43, 95% confidence interval: 0.13-0.66, P=.007). The extent of pentraxin 3 and inflammatory cell infiltrates in the aorta was similar in rheumatoid arthritis and non-rheumatoid-arthritis patients, but rheumatoid arthritis patients had more fibrosis and a lower proportion of T-cells in inflammatory cell infiltrates. In the internal thoracic artery, pentraxin 3 occurred only in 36% patients, and inflammatory cell infiltrates and fibrosis occurred in none. CONCLUSIONS: Pentraxin 3 depositions in the outer aortic layers are common and are related to the local inflammation. On the other hand, they occur less frequently in the internal thoracic artery, i.e., a vessel highly resistant to atherosclerosis. Rheumatoid arthritis patients had more pronounced fibrosis in the aortic specimens and a different leukocytic response than non-rheumatoid-arthritis patients. In theory, pentraxin 3 might modulate the inflammatory process involved in the pathogenesis of cardiovascular disease and represent a target for new therapies.

Antibodies to common infectious agents in coronary artery disease patients with and without rheumatic conditions.

OBJECTIVES: The mechanism linking inflammation to atherosclerosis is unknown. We have previously demonstrated a high occurrence of inflammation in the aortic adventitia of patients with coronary artery disease (CAD), which was more pronounced in patients with inflammatory rheumatic diseases (IRDs), and which might be involved in the pathogenesis of cardiovascular disease. In theory, infections might play a role in the pathogenesis of vascular inflammation or atherosclerosis, or both. This study compared seropositivity and the burden of several common infections in patients with CAD, both with and without IRD, and in healthy controls (HCs). Moreover, we looked for relationships between the examined antibodies and inflammatory infiltrates in the aortic adventitia. METHODS: We examined sera for Chlamydophila pneumoniae, Mycoplasma pneumoniae, Helicobacter pylori, CMV, Streptococcus pyogenes, parvovirus B19, HBV and HCV with commercially available serological tests in 67 patients with IRD, 52 patients without IRD and 30 HCs. RESULTS: We observed neither any statistically significant differences in the examined antibodies between the groups nor a difference in the burden of infection. Except for a protective effect of mycoplasma immunoglobulin A (IgA), we did not find any other associations between the examined antibodies and the occurrence of aortic adventitial mononuclear cell infiltrates. CONCLUSION: Our study does not support the notion that chronic infections or infectious burden contribute to accelerated occurrence of CAD in IRD. Mycoplasma IgA was related to a lower occurrence of aortic adventitial inflammation.

Increased levels of serum pentraxin 3, a novel cardiovascular biomarker, in patients with inflammatory rheumatic disease.

OBJECTIVE: Pentraxin 3 (PTX3), a key component of innate immunity, is a strong marker of disease severity in coronary artery disease (CAD). The aim of this study was to compare levels of serum PTX3 in CAD patients with and without inflammatory rheumatic disease (IRD) and in healthy controls. METHODS: We examined 69 patients with IRD (CAD/IRD group) and 53 patients without IRD (CAD/non-IRD) referred to coronary artery bypass grafting, and 30 healthy controls. RESULTS: The mean +/- SD serum PTX3 level in the CAD/IRD group was 1.96 +/- 0.98 ng/ml; this was statistically significantly higher than that of the CAD/non-IRD (1.41 +/- 0.74 ng/ml) and healthy control (1.21 +/- 0.59 ng/ml) groups. In contrast to most other IRDs, serum PTX3 levels were relatively low in patients with systemic lupus erythematosus (SLE) and other systemic connective tissue diseases. In sex- and age-adjusted analysis, IRD, acute coronary syndromes, and low alcohol intake were associated with higher serum PTX3 levels. CONCLUSION: CAD patients with IRD had higher mean serum PTX3 levels than patients without IRD and healthy controls. In addition, acute coronary syndromes and low alcohol intake independently predicted higher serum PTX3 levels. Higher serum PTX3 levels in IRD may be related to the higher cardiovascular risk of IRD patients. Circulating PTX3 could likely be used as a biomarker for severity of cardiovascular disease in IRDs; its importance, however, might be limited in SLE and related disorders.