OBJECTIVE:Phospholipid transfer protein (PLTP) facilitates cholesterol efflux from cells, intravascular HDL remodelling and transfer of vitamin E and endotoxin. In humans, the relationship of PLTP to atherosclerosis is unknown. However, strong coronary risk factors like obesity, diabetes, cigarette smoking and inflammation increase circulating levels of active PLTP. The aim of the present, cross-sectional study was to analyze the relationship of PLTP to peripheral arterial disease, a marker of generalized atherosclerosis, independently of potentially confounding factors like obesity, diabetes and smoking. METHODS:We performed a case control study in 153 patients with symptomatic peripheral arterial disease (PAD) and 208 controls free of vascular disease. Smokers and patients with diabetes mellitus were excluded. A lipoprotein-independent assay was used for measurement of circulating bioactive PLTP and an ELISA utilizing a monoclonal antibody was used to analyze PLTP mass. RESULTS:PLTP activity was significantly decreased in patients with PAD 5.5 (4.6-6.4)(median (25th-75th percentile)) versus 5.9 (5.1-6.9) micromol/mL/h in controls (p=0.001). In contrast, PLTP mass was similar in patients with PAD 8.5 microg/mL (7.3-9.5) and in controls 8.3 microg/mL (6.9-9.7) (p=0.665). Multivariate logistic regression analysis revealed that PLTP activity is independently associated with the presence of PAD. PLTP activity was similar in patients with and without lipid-lowering drugs (p=0.396). CONCLUSION:Our results show that in non-diabetic, non-smoking subjects low rather than high PLTP activity is a marker for the presence of peripheral arterial disease and that distribution of PLTP between high-activity and low-activity forms may be compromised in atherosclerosis.

Background. Hepatic lipase plays a key role in the metabolism of pro-atherogenic and anti-atherogenic lipoproteins affecting their plasma level as well as their physico-chemical properties. We hypothesized single nucleotide polymorphisms in the promoter region of the hepatic lipase gene to be associated with an increased risk for peripheral arterial disease (PAD).Methods. A total of 241 patients with PAD and 241 controls matched for sex and age (+/- 2 years) were genotyped cross-sectionally for the -250 single nucleotide polymorphism in the hepatic lipase promoter.Results. The frequency for the -250A allele in patients with PAD was 0.203, whereas it was 0.147 in the controls (P = 0.022). Hepatic lipase promoter polymorphism distribution remained significantly different between cases and controls after multivariate logistic regression analysis (P = 0.021). The odds ratio of the -250A hepatic lipase allele for the PAD was 1.69 (95% confidence interval of 1.08-2.64), when adjusted for current smoking, arterial hypertension, cholesterol, triglycerides, HbA(1C), total homocysteine and high sensitivity C-reactive protein.Conclusion. Previous data in patients with ischaemic heart disease have suggested a pro-atherogenic role of low hepatic lipase levels. Our results extend these data to the vascular territory of the lower limbs, such that hepatic lipase promoter variation represents a genetic risk factor of PAD.

OBJECTIVES:The objective of this prospective study was to evaluate the relation between high lipoprotein(a) levels and thrombotic and restenotic events after coronary stent implantation.BACKGROUND:Lipoprotein(a) may promote atherogenesis, coronary thrombosis and restenosis after balloon angioplasty, but the clinical significance remains unclear.METHODS:The study included 2,223 consecutive patients with successful coronary stent placement. According to the serum level of lipoprotein(a), patients were divided in two groups: 457 patients of the highest quintile formed the high lipoprotein(a) group, and 1,766 patients of the lower four quintiles formed the low lipoprotein(a) group. Primary end points were the incidence of angiographic restenosis at six months and the event-free survival at one year. Secondary end point was the incidence of angiographic stent occlusion.RESULTS:Early stent occlusion occurred in four of the 457 patients (0.9%) with high and 37 of the 1,766 patients (2.1%) with low lipoprotein(a) levels, odds ratio of 0.41 (95% confidence interval, 0.15 to 1.16). Angiographic restenosis occurred in 173 of the 523 lesions (33.2%) in the high lipoprotein(a) group and 636 of the 1,943 lesions (32.7%) in the low lipoprotein(a) group, odds ratio of 1.02 (0.83 to 1.25). The probability of event-free survival was 73.0% in the high lipoprotein(a) group and 74.8% in the low lipoprotein(a) group (p = 0.45). On the basis of the findings in the low lipoprotein(a) group, the power of this study to detect a 25% increase in the incidence of restenosis and adverse events in the group with elevated lipoprotein(a) was 90% and 75%, respectively.CONCLUSIONS:Elevated lipoprotein(a) levels did not influence the one-year clinical and angiographic outcome after stent placement. Thrombotic events and measures of restenosis were not adversely affected by the presence of high lipoprotein(a) levels.

A consecutive series of 132 patients with total chronic coronary occlusions were compared with 1,966 patients with stenotic lesions in terms of angiographic and clinical outcome. We concluded that patients with chronically occluded coronary lesions present a higher rate of target lesion revascularizations and angiographic restenosis than patients with stenotic lesions.

Objectives. The objectives of this study were to analyze the clinical and angiographic outcome of diabetic patients with successful coronary stent placement and to compare these results with those achieved after stenting in nondiabetic patients.Background. The outcome of diabetic patients treated with stent placement due to coronary artery disease has not been assessed comprehensively.Methods. This study analyzes a consecutive series of patients with successful stent placement comprising 715 patients with diabetes and 2,839 patients without diabetes. Clinical one year follow-up and angiographic control at 6 months were part of the protocol. Death, myocardial infarction and target lesion revascularization were considered as adverse events. An automated edge detection system was used for the angiographic assessment. The primary clinical endpoint was event-free survival at one year. The primary angiographic endpoint was restenosis rate at 6 months (greater than or equal to 50% diameter stenosis).Results. Event free survival was significantly lower in diabetic than in nondiabetic patients (73.1 vs. 78.5%, p < 0.001). Survival free of myocardial infarction was also significantly reduced in the diabetic group (89.9 vs. 94.4% in nondiabetics, p < 0.001). The incidence of both restenosis (37.5 vs. 28.3%, p < 0.001) and stent vessel occlusion (5.3 vs. 3.4%, p = 0.037) was significantly higher in diabetic patients. Diabetes was identified as an independent risk factor for adverse clinical events and restenosis in multivariate analyses.Conclusions. Patients with diabetes mellitus have a less favorable clinical outcome at one year after successful stent placement as compared to the nondiabetic patients. The clinical follow-up was characterized by a higher incidence of death, myocardial infarction and reinterventions. Diabetic patients also demonstrated an increased risk for restenosis. (J Am Coll Cardiol 1998;32:1866-73) (C) 1998 by the American College of Cardiology.