Paraoxonase-1 (PON1) promoter region polymorphisms, serum PON1 status and coronary heart disease.

INTRODUCTION: Serum paraoxonase-1 (PON1) retards the oxidation of low-density lipoprotein and cell membranes and is atheroprotective. Polymorphisms in the promoter region of the PON1 gene have been shown to affect serum PON1 levels and have been related to the presence of coronary heart disease (CHD) in some studies. However, contradictory results have been reported with regard to promoter region polymorphisms and CHD presence; therefore we have re-examined the effects of the C-108T and G-909C promoter polymorphisms on PON1 levels and the presence of CHD in a large case-control study. MATERIAL AND METHODS: Paraoxonase-1 activity, concentration and the C-108T and G-909C polymorphisms were measured in 417 people with CHD and 282 healthy controls, in a case control study. RESULTS: Paraoxonase-1 activity and concentration were significantly lower in the CHD population compared to controls regardless of their C-108T and G-909C genotype (p < 0.001). Paraoxonase-1 activity was significantly different in the C-108T genotypes in both the control and CHD groups in the order TT < TC < CC (p < 0.01). Paraoxonase-1 concentration was significantly different in the CHD group only in the G-909C genotype in the order GG > GC > CC (p < 0.01). Haplotype analysis revealed no consistent patterns of PON1 activity in the CHD population; however, in the controls PON1 activity differed between haplotypes GGCC > GGTC > GGTT (p < 0.05) and GCCC > GCTC > GCTT (p < 0.02). Neither promoter polymorphism was associated with CHD presence. CONCLUSIONS: Paraoxonase-1 status was significantly lower in people with CHD and was affected by the promoter region polymorphisms.

Prognostic value of demographic factors, pre-test probability scoring, exercise test diagnosis, and inability to exercise in patients with recent onset suspected cardiac chest pain.

AIMS: To assess the prognostic value of an inconclusive exercise test or inability to exercise in patients with recent onset suspected cardiac chest pain and to determine the independent predictors of events in these patients. METHODS: This was an observational follow-up study of patients presenting to a rapid access chest pain clinic with a history of recent-onset suspected cardiac chest pain as referred by the family practitioner. The main outcome measure was a composite endpoint of death and acute coronary syndrome hospital admission. RESULTS: The study cohort consisted of 1851 patients in whom a total of 147 events were recorded during a mean follow-up period of 4.1 ± 1.1 years. Those with events were significantly older (65.1 ± 12.5 years versus 56.4 ± 13.2 years, p < 0.001), had higher mean pre-test probability of coronary artery disease (CAD), and had higher prevalence of diabetes (18.4% vs. 13.6%, p < 0.001), hypertension (55.8% vs. 38.7%, p < 0.001), and smoking (36.7% vs. 25.4%, p = 0.03) than those without events. These patients were also more likely to have a positive exercise electrocardiogram (ECG) (15.6% vs. 8.6%, p < 0.001) or not have a diagnostic exercise test because of an inconclusive result or inability to exercise (60.5% vs. 28.6%, p < 0.001). Cox multivariate regression analysis showed that age (hazard ratio, HR 1.03, p < 0.001), pre-test probability of CAD (HR 1.08, p = 0.04), positive exercise ECG (HR 2.94, p < 0.001), and an inconclusive test or inability to exercise (HR 3.45, p < 0.001) were independent predictors of events. CONCLUSIONS: In patients with recent onset suspected cardiac chest pain, not having a diagnostic exercise ECG because of an inconclusive test or inability to exercise is an independent predictor of events and has similar prognostic implications to a positive exercise ECG. In addition, pre-test probability estimation at baseline is a robust indicator of clinical outcome. Future models of care need to incorporate early and increased access to non-exercise cardiac imaging techniques in order to meet the needs of this high-risk subgroup of patients.

Edge-to-edge repair of tricuspid valve in a corrected transposition of the great vessels.

We describe the case of a 27-year-old Caucasian woman with corrected transposition of the great vessels, who presented with cardiac failure. She had severe regurgitation of the systemic tricuspid valve with a huge annulus that was not suitable for annuloplasty. She underwent a successful repair using the Alfieri edge-to-edge technique and was asymptomatic 15 months after surgery. Such a repair has not been reported in the past.

Hyperinsulinemia, insulin resistance, and circulating oxidized low density lipoprotein in women with systemic lupus erythematosus.

OBJECTIVE: Women with systemic lupus erythematosus (SLE) have increased risk of coronary heart disease (CHD) that is not fully explained by the classic CHD risk factors. Insulin resistance is an established risk factor for CHD in the general population. We compared insulin secretion and sensitivity in patients with SLE and healthy controls, and assessed the prevalence of the metabolic syndrome in women with SLE and its relation to circulating oxidized low density lipoprotein (ox-LDL). METHODS: Fasting insulin, glucose, and lipid profiles were measured in nondiabetic women with SLE (>or= 4 revised 1997 criteria) not undergoing antimalarial therapy (n = 44), and in age matched controls recruited from the hospital staff and the local community (n = 45). Using the Homeostatic Model Assessment equations, insulin sensitivity (HOMA-S) and pancreatic beta cell function (HOMA-B) were calculated from fasting insulin and glucose. The metabolic syndrome, defined according to the Adult Treatment Panel (ATP III) criteria, was determined in a consecutive series of 61 women with SLE. RESULTS: Patients with SLE had significantly higher fasting insulin [median (range) 10 (2.8-38) vs 6.6 (3.1-26) mU/l; p < 0.01], higher pancreatic beta cell function (HOMA-B) [165 (54-1567) vs 111 (28-653); p < 0.01], and lower insulin sensitivity (HOMA-S) [0.46 (0.09-1.9) vs 0.73 (0.16-1.3); p < 0.01]. SLE patients also had significantly higher triglycerides (p < 0.01) and lower high density lipoprotein cholesterol (p < 0.01) than controls. HOMA-S did not correlate with disease activity or steroid therapy, but was associated with components of the insulin resistance syndrome. HOMA-S showed a significant negative correlation with levels of ox-LDL in patients, but not in controls. Eleven (18%) patients had the metabolic syndrome. Again, this was not related to current steroid therapy. SLE patients with the metabolic syndrome had no difference in LDL, but had significantly higher levels of ox-LDL. CONCLUSION: Nondiabetic patients with SLE have evidence of significant decrease in sensitivity to insulin, and overall this population has a high prevalence of the metabolic syndrome (18%). Insulin resistance in the context of SLE was not strongly related to current or recent steroid therapy; it was, however, associated with higher levels of ox-LDL. Insulin resistance may therefore represent an additional CHD risk factor in patients with SLE.

Right ventricular failure due to postpericardiotomy syndrome following transvenous dual chamber permanent pacemaker implantation.

"Pericardial effusion and tamponade are recognised complications of permanent transvenous pacemakers implantation. This is more common when active fixation leads are used. We describe a patient who developed right ventricular failure with significant pericardial effusion following permanent transvenous pacemaker implantation."