The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating five overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBPα expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3'UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis.

Background. The impact of thyroid disease on patients undergoing coronary artery bypass grafting has been reported in only small series of selected patients. Methods. We investigated 30-day mortality of patients on thyroxine replacement therapy undergoing isolated coronary artery bypass grafting from 1993 to 2000 and identified variables of importance for outcome. Results. A total of 3,631 patients (606 women) had isolated coronary artery bypass grafting of whom 58 patients (30 women) were treated for hypothyroidism. The mortality rate was higher among women with thyroxine replacement (16.7%, 95% confidence interval [CI] 5.6 to 34.7) than those without thyroxine replacement (5.9%, 95% CI 4.1 to 8.2; p = 0.02) and no difference between men with (3.6%, 95% CI 0.1 to 17.8) and without (2.6%, 95% CI 2.0 to 3.2) thyroxine treatment (p = 0.8). Intake of diuretics (p < 0.001) was directly associated with mortality whereas intake of aspirin (p = 0.01), levothyroxine dose (p = 0.03), and serum thyroxine level (p = 0.01) were inversely associated with mortality among women on thyroxine replacement. Conclusions. Women on thyroxine replacement therapy undergoing coronary artery bypass grafting had an increased mortality rate. We speculate that insufficient thyroid hormone replacement could partly play a role in this outcome.

OBJECTIVE:South Asian patients in the UK have a higher mortality rate after coronary artery bypass grafting (CABG) than Caucasian patients. As coronary artery size has been shown to correlate to outcome from bypass grafting, it has been suggested that smaller coronary arteries in South Asians as compared to Caucasians could contribute to a poorer outcome in the Asian population. We aimed to measure coronary artery size and disease in matched South Asian and Caucasian men undergoing first time coronary artery bypass grafting. METHODS:Coronary arteriograms from 53 matched first generation South Asian and Caucasian men were examined. The patients had no history of myocardial infarction, coronary revascularisation, familial dyslipidaemia, diabetes or renal disease. They were individually matched for age, height, weight, body mass index and body surface area. Thereafter, coronary artery diameters and significant (> or =50%) diameter stenoses were measured in a blinded fashion using quantitative coronary angiography (QCA). RESULTS:In South Asian men, diameters of the left main stem (LMS) and the proximal left anterior descending, the circumflex and the right coronary arteries were 4.6+/-0.9 mm, 3.5+/-0.8 mm, 3.4+/-0.8 mm and 3.5+/-0.8 mm, respectively. The corresponding arterial diameters among Caucasian men (4.5+/-0.9 mm, 3.5+/-0.7 mm, 3.5+/-0.8 mm and 3.8+/-0.8 mm) did not differ from those in South Asians. There was no difference in the number of significant coronary artery stenoses between the two groups and no difference in bypass and cross-clamp times or in adverse outcome (one from each group died after coronary artery bypass grafting). CONCLUSION:Proximal coronary artery size and number of significant coronary stenoses did not differ between matched pairs of South Asian and Caucasian men using strict inclusion/exclusion criteria.

Infectious disease can be linked to social deprivation. We investigated whether postoperative infection with meticillin-resistant Staphylococcus aureus (MRSA) is related to socioeconomic background. Patients were stratified by social deprivation according to postcode. In a consecutive series of 1739 UK residents undergoing isolated coronary artery bypass grafting, 23 (1.3%) were infected with MRSA. We noted a graded relation between incidence of infection and social deprivation. Patients from the most deprived areas had a seven-fold higher infection rate (13 of 579 [2.2%]) than those from the least deprived areas (two of 580 [0.3%]; p=0.0040). Patients with MRSA infection had a six-fold higher mortality rate and a longer hospital stay than patients with no such infection. Our findings suggest that patients from deprived areas might be especially susceptible to postoperative infection with MRSA.

Chronic low-grade inflammation has been associated with the development of atherosclerosis ( 1 Ross R. Atherosclerosis an inflammatory disease. N Engl J Med. 1999; 340: 115-126 Crossref PubMed Scopus (19694) Google Scholar ). Accordingly, increased levels of various plasma markers of inflammation, including leukocyte count, have been shown to predict coronary and cerebrovascular events ( 2 Danesh J. Collins R. Appleby P. Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998; 279: 1477-1482 Crossref PubMed Scopus (1876) Google Scholar , 3 Blankenberg S. Rupprecht H.J. Bickel C. et al. Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation. 2001; 104: 1336-1342 Crossref PubMed Scopus (496) Google Scholar ). However, markers of inflammation are also elevated in the presence of infections, unspecific inflammation, as well as a variety of diseases and conditions ( 4 Dale D.C. Neutropenia and neutrophilia. in: Beutler E. Lichtman M.A. Coller B.S. Kipps T.J. Seligsohn U. Williams Hematology. 6th ed. McGraw-Hill, New York, New York2001: 823-834 Google Scholar ), and they have been associated with risk factors such as smoking and obesity that may influence outcome in cardiovascular disease ( 2 Danesh J. Collins R. Appleby P. Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998; 279: 1477-1482 Crossref PubMed Scopus (1876) Google Scholar ). The importance of increased levels of inflammatory markers for outcome in relation to a major cardiac intervention is not known. We therefore evaluated the association between a single, preoperative, baseline leukocyte count before coronary artery bypass grafting and operative mortality.

We did an observational study in 2059 patients undergoing coronary artery bypass surgery to assess the effect of haemoglobin concentration on in-hospital mortality. We noted that individuals with a preoperative haemoglobin concentration of 100 g/L or less had a five-fold higher in-hospital mortality rate after surgery than those with a higher haemoglobin concentration, despite having had blood transfusions or the pump primed with blood preoperatively as a routine precaution. Our findings suggest that a low haemoglobin concentration is a marker of disease severity or comorbidity that has a major effect on survival rate.

OBJECTIVE:To investigate the relationship between admission plasma glucose and 30-day mortality after primary isolated coronary artery bypass grafting (CABG) in nondiabetic patients. RESEARCH DESIGN AND METHODS:All nondiabetic patients with admission plasma glucose measurement undergoing primary isolated CABG from 1993 to 1997 were included in this study. RESULTS:In 878 consecutive patients (155 women), overall mortality was 3.4% (95% CI 2.3-4.8). The mortality rate in women (n = 11; 7.1%, 3.6-12.3) was higher than in men (n = 19; 2.6%, 1.6-4.1) (P = 0.01). There was a positive correlation between plasma glucose and 30-day mortality among women only (P = 0.0001). There was a higher mortality rate in the upper two glucose quartiles (11.7%, 5.5-21.0) compared with the lower two quartiles (2.6%, 3.0-8.9) in the female patients (P = 0.03); a plasma glucose of 6.0 mmol/l separated high- and low-mortality groups. Furthermore, women in the upper two glucose quartiles had a fourfold higher mortality rate than men in the similar quartiles (P = 0.002). Among men, there was no difference in mortality rate across glucose quartiles. In a multivariate analysis, admission plasma glucose, history of thyroid disease, left ventricular ejection fraction <0.35, operation bypass time, and perioperative myocardial infarction were independently associated with mortality. CONCLUSIONS:Women with admission plasma glucose < or =6.0 mmol/l and men across the whole range of glucose values had similar mortality rates after CABG. The surplus female mortality was found only in subjects with plasma glucose >6 mmol/l. Further studies are needed to appraise the possible influence of glucose status on outcome from CABG in nondiabetic subjects.

In a consecutive series of 436 Indian Subcontinent Asians and 1,458 Caucasians undergoing primary isolated coronary artery bypass grafting, the mortality rate was twofold higher in Asians than in Caucasians, which resulted mainly from a mortality difference between men in the 2 groups. Diabetics had a higher mortality rate than nondiabetics. and diabetes, 2.5 times more frequent in Asians than in Caucasians, was an independent predictor of death only in Asians and may in part explain the mortality difference.