Background-Paraoxonase is an HDL-associated enzyme that protects lipoproteins from oxidative modifications.Smoking is a major cardiovascular risk factor that promotes lipid peroxidation. Cigarette smoke has been shown in vitro to inhibit paraoxonase. The present study examined the hypothesis that smoking is associated with modulated serum activities and concentrations of paraoxonase. Methods and Results-Coronary artery disease was assessed with the use of coronary arteriography in participants recruited from a hospital cardiology division. Medical and lifestyle data were obtained, and a fasting blood sample was provided. Three smoking categories were established (never, ex-smokers, and current smokers), and serum paraoxonase variables were compared among them. The activities and concentrations of paraoxonase were significantly lower in current than in never smokers. Ex-smokers had values comparable to those of never smokers. Ex-smokers who had recently stopped (Ͻ3 months) had activities and concentrations comparable to those of current smokers; values returned to the levels of never smokers within 2 years of cessation of smoking. Smoking status was an independent determinant of paraoxonase activity and concentration in multivariate analysis. Finally, lower paraoxonase was associated with more severe coronary disease and a reduced capacity to protect LDL from oxidation. Conclusions-Smoking is independently associated with significant decreases in serum paraoxonase activities and concentrations, which normalize within a relatively short time of cessation. Lower serum paraoxonase is linked to more severe coronary artery disease and a lower antioxidant capacity. The data are consistent with the hypothesis that smoking modifies serum paraoxonase such that there is an increased risk of coronary artery disease due to a diminished capacity to protect lipoproteins from oxidative stress.
MIBG H/M (planar) and relative segmental uptake (SPECT) show a low interindividual and within-subject variability. This enables the detection of small (regional) variations in myocardial sympathetic nervous function, especially to monitor the effect of therapeutic interventions in patients with various cardiac diseases.
This study tested the hypothesis that promoter polymorphism T(-107)C of the human paraoxonase gene (PON1) is associated with risk of coronary disease. Participants (n=897) were recruited from a cardiology department. All underwent coronary arteriography and were defined as coronary artery disease positive (n=699) or negative (n=198). No association of the promoter genotypes with coronary disease was observed in the overall population, but the high expressor genotype (-107CC) was associated with decreased risk of disease in patients aged 60 years or under in univariate and multivariate analysis independently of established risk factors. A significant deficiency in paraoxonase relative to cholesterol was apparent in patients, even when they were matched with controls for total and low-density lipoprotein cholesterol levels. The -107 polymorphism was not associated with risk in older patients (61 years or over). Age was negatively associated with serum concentrations and activities of paraoxonase; serum paraoxonase was significantly higher in those aged under 61 years than in those aged 61 or over. Age was an independent predictor of paraoxonase concentrations. The results indicate that in this population of patients the promoter polymorphism T(-107)C of the PON1 gene is an independent risk factor for coronary disease in those 60 years or younger. The data are consistent with the hypothesis that lower expression of this anti-oxidant enzyme increases risk of coronary disease. Ageing has also been identified as an independent determinant of serum paraoxonase levels. Ageing is correlated with reduced serum paraoxonase levels, which may compromise the protective influence of enzyme. The results are consistent with the contention that the protective, anti-oxidant capacity of high density lipoproteins is at least in part genetically determined.
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