[Association between variants of lipoprotein lipase and coronary heart disease in a Tunisian population]. / Association entre des variations de la lipoprotéine lipase et la maladie coronarienne dans une population tunisienne.

OBJECTIVE: Coronary artery disease (CAD) is a complex multifactorial disease due to the interaction of multiple genes variations and environmental factors. Genetic variants of lipoprotein lipase (LPL), a key enzyme in the hydrolysis of triglyceride rich particles, may contribute to CAD. We analysed here the frequency of LPL variants (p.Asp9Asn, p.Asn291Ser and p.Ser447X) in a Tunisian population as well as their association with circulating lipid level and risk of CAD. PATIENTS AND METHODS: LPL variations were investigated by PCR-RFLP and lipid parameters were measured in 135 patients and 109 controls. RESULTS: The frequency of the p.Asp9Asn variation was 10.37% in CAD patients versus 3.66% in controls. The frequency for the p.Ser447X variation was 8.8% in CAD patients versus 13.7% in controls. There was no significant association between these two variants and CAD. The p.Asn291Ser mutation variation was absent in this population. In healthy subjects, heterozygote carriers of the p.Asp9Asn substitution had a significant increase level of total cholesterol (4.2±0.9mmol/L vs 5.6±1.2mmol/L; P=0.01) and a decreased level of HDL-cholesterol (1.36±0.3mmol/L vs 0.93±0.1mmol/L; P=0.045). CONCLUSION: There was no significant association between genetic variants of the LPL gene and CAD in this Tunisian population. The very low frequency of the p.Asn291Ser variation may be an ethnic specificity of Tunisians.

+294T/C polymorphism in the PPAR-delta gene is associated with risk of coronary artery disease in normolipidemic Tunisians.

Peroxisome proliferator-activated receptor delta (PPAR-delta) is a transcription factor implicated in metabolism and inflammation. The +294T/C polymorphism in the PPAR-delta gene is associated with risk of coronary artery disease (CAD) in dyslipidemic women and hypercholesterolemic men. Whether this polymorphism influences the risk of CAD in the absence of dyslipidemia was not known, so we investigated a possible association of this polymorphism with plasma lipid and lipoprotein levels and with risk and outcome of CAD in a normolipidemic Tunisian population. Genotyping was performed by PCR-RFLP in 112 CAD patients and 113 healthy volunteers. The C-allele was significantly more frequent in patients than in controls (0.320 vs 0.189, P = 0.001). This association remained significant after adjustment for age, gender, body mass index, smoking, hypertension, and high-density lipoprotein cholesterol. Subjects carrying either one or two copies of the C-allele had a 2.7-fold higher risk of CAD than subjects homozygous for the T-allele. PPAR-delta genotypes were not associated with lipoprotein concentrations or outcome of CAD. We conclude that PPAR-delta +294T/C polymorphism is an independent risk factor of CAD in normolipidemic Tunisian subjects. The lack of association with lipoprotein concentrations suggests that the effect of the polymorphism on CAD is not mediated through lipoprotein levels in this population and that it may influence the atherosclerotic process through mechanisms involving inflammation.

Long-term invasive and noninvasive results of percutaneous balloon pulmonary valvuloplasty in children, adolescents, and adults.

BACKGROUND: Short-term and mid-term results of percutaneous balloon pulmonary valvuloplasty (BPV) are well known. However, data documenting long-term effectiveness of BPV are scarce. METHODS AND RESULTS: The long-term results of 62 patients were assessed by catheterization and Doppler echocardiography 1 to 10 years (mean 6.4 +/- 3.4) after BPV. Mean age of the patients was 13.5 +/- 10.5 years (range 9 months to 44 years). Twenty patients were 16 years of age or older. Right ventricular peak systolic pressure was systemic or suprasystemic in 72% of patients. A double-balloon technique was used in 29 patients. The balloon-to-pulmonary valve diameter ratio was 1.4 +/- 0.38 (range 1 to 1.8). Total systolic transpulmonary pressure gradient in excess of 50 mm Hg in all patients before BPV decreased from 98 +/- 40 to 32 +/- 23 immediately after BPV and to 19 +/- 9 mm Hg at follow-up (P <.001). Infundibular gradient increased from 8 +/- 10 to 14 +/- 24 mm Hg after BPV and fell to 1 +/- 4 mm Hg at follow-up (P <.01). In 16 patients it was >/=20 mm Hg and virtually disappeared spontaneously in all at follow-up. The valvar gradient fell from 93 +/- 39 to 19 +/- 11 (P <.001) and was 18 +/- 9 mm Hg at follow-up. It remained unchanged in 3 patients (range 36 to 45 mm Hg). In 3 (4.8%) other patients, a new gradient >35 mm Hg developed that was >/=50 mm Hg in all 3. Among 5 patients having dysplastic valves, 3 had a gradient >35 mm Hg. There were no predictors of a gradient >35 mm Hg at long-term follow-up by univariate or multivariate Cox proportional hazards analysis. Mild to moderate pulmonary regurgitation was present in 39% of patients. On electrocardiography, right ventricular hypertrophy decreased significantly in 90% of patients. CONCLUSIONS: BPV as a treatment of typical pulmonic valve stenosis produces excellent long-term results. Restenosis is rare (4.8%) and occurs more frequently in patients with dysplastic valves. There is a constant spontaneous regression of associated infundibular obstruction.

Stent implantation in acute myocardial infarction.

Among 138 patients treated with coronary angioplasty during acute myocardial infarction (AMI), 35 (25%) had stent implantation. Mean age was 56 years and 83% were men. Mean onset of chest pain was 6.0 +/- 5.3 hours, and previous thrombolytic therapy was given to 10 patients (29%). Infarct location was anterior in 19 (54%), inferior in 14 (40%), and lateral in 2 patients (6%). Thrombolysis in Myocardial Infarction trial flows 0,1, and 2 were seen in 24 (69%), 6 (17%), and 5 patients (14%), respectively. The culprit vessel was the left anterior descending artery in 18 (51%), right coronary artery in 14 (40%), left circumflex in 2 (6%), and left main coronary artery in 1 patient (3%). Mean vessel diameter was 3.3 +/- 0.3 mm. Indications were: primary in 5 (14%), suboptimal result in 8 (23%), nonocclusive dissection in 14 (40%), and occlusive dissection in 8 patients (23%). Angiographic thrombus after initial angioplasty was present in 12 patients (34%). A total of 46 stents were implanted; mean balloon diameter and pressure were 3.4 +/- 0.4 mm and 15.5 +/- 2.2 atm, respectively. Residual diameter stenosis was 4 +/- 7%. There were 2 deaths; sudden 1, and after elective coronary artery bypass grafting in the other; 2 patients (6%) had groin hematomas. Mean hospitalization was 9.9 +/- 5.0 days. Repeat angiography revealed no stent occlusion. With initial intravenous heparin for 3 to 7 days, all patients received aspirin and ticlopidine for 1 month. Thus, AMI is not a contraindication for stent implantation. The benefits of stenting are a high success rte, low residual diameter stenosis, and low incidence of in-hospital recurrent ischemia. Reduction in restenosis rate in this setting is likely but remains to be determined.