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Abstract-Human paraoxonase (PON1) is a calcium-dependent esterase closely associated with high density lipoprotein (HDL)-containing apolipoprotein AI (apoAI), which has been shown to confer antioxidant properties to HDL. PON1 has been recently implicated in the pathogenesis of atherosclerosis. Low PON1 activities have been found in familial hypercholesterolemia (FH) and diabetes mellitus. We have undertaken a study of the effect of the lipid-lowering drug simvastatin on serum PON1 activity (in relation to paraoxon and arylesterase activity), on apoAI-containing and apolipoprotein B (apoB)-containing lipoproteins, and on lipid peroxide concentrations in 64 (39 women and 25 men) unrelated FH patients. We have also analyzed the influence of the PON1-192 and PON1-55 genetic polymorphisms on the response of PON1 activity to simvastatin therapy. A venous blood sample for a baseline analysis and another after 4 months of simvastatin therapy at a dosage of 20 mg per day were taken. The major effect of simvastatin on lipid traits was to decrease serum cholesterol, low density lipoprotein (LDL) cholesterol, and lipid peroxide concentrations by 19.9%, 26.3%, and 37.3%, respectively. There was also a significant decrease in serum apoB, LDL apoB, and triglyceride concentrations (20.5%, 21.1%, and 15.6%, respectively). Conversely, simvastatin had no significant influence on very low density lipoprotein-lipid content, HDL cholesterol, apoAI concentrations, and lipoprotein AI and AI:AII particles. Remarkably, serum PON1 activity toward paraoxon significantly increased during treatment with simvastatin (168.7Ϯ100.3 U/L before therapy versus 189.5Ϯ116.5 U/L after therapy, Pϭ0.005). Arylesterase activity displayed only a nonsignificant trend to increase after therapy. Whereas PON1 activity levels were significantly lower in FH patients before simvastatin therapy compared with those of 124 normolipidemic subjects (168.7Ϯ100.3 versus 207.6Ϯ125.2 U/L, respectively; PϽ0.05), this difference disappeared after simvastatin therapy. After simvastatin therapy, a significantly negative correlation between PON1 activity and lipid peroxide concentration was observed (rϭϪ0.35, Pϭ0.028). The latter also strongly correlated with LDL cholesterol concentration (rϭ0.64, PϽ0.001). Serum PON1 activity levels were significantly lower in the low-activity PON1-192 QQ and PON1-55 M carriers than in R carriers and in LL carriers, respectively. No significant differences were found in the therapeutic response of PON1 activity between genotype groups (8.5% and 11.1% increase for QQ homozygous and R-carrier FH patients, respectively, and 12.7% and 9.5% increase for LL homozygotes and M carriers, respectively). We conclude that simvastatin may have important antioxidant properties through increasing serum PON1 activity, perhaps as a consequence of reducing oxidative stress, by a mechanism independent of apoAI-containing lipoprotein concentration and without the influence of PON1-192 and PON1-55 genetic polymorphisms. Further studies are clearly warranted to c...

Study objective-To establish the prevalence of main cardiovascular risk factors in the province of Gerona, where the incidence of myocardial infarction is known to be low. Design-This was a cross sectional study of prevalence of cardiovascular risk factors conducted on a large random population sample. Setting-The province of Gerona, Spain. Participants-Two thousand four hundred and four eligible inhabitants of Gerona aged between 25 and 74 years were randomly selected for a multi-stage sample stratified by age and sex. The following were standardly measured: lipids (total cholesterol, high density, low density, lipoprotein (a) and triglycerides), fibrinogen, basal glycaemia, arterial pressure, anthropometric variables, smoking, history of angina (Rose questionnaire), and a medical history questionnaire. Population measurements were standardised for the world population of 24 to 74 years of age. Results-The participation rate was 72.7% (1748). Total mean cholesterol was 5.69 mmol/l in men and 5.61 mmol/l in women and mean high density cholesterol was 1.22 mmol/l and 1.47 mmol/l, respectively. Median lipoprotein (a) was 0.22 g/l. These three lipids increased significantly with age. Mean fibrinogen was 2.92 g/l in men and 3.09 g/l in women, and was higher in smokers. The prevalence of hypertension (systolic arterial tension >140 mm Hg or diastolic >90 mm Hg or drug treatment) was 31.3% in men and 27.7% in women. The proportion of male smokers was 33.8% and female smokers 22.7%. The proportion of female smokers in the 25-34 year age group exceeded that of the remaining age groups for both men and women. Conclusions-The prevalence of cardiovascular risk factors in Gerona is relatively high for the low myocardial infarction incidence typical of the area, although similar to that of other Spanish areas. The factors that confer suYcient protection to compensate for the eVect of the prevalence of these risk factors remain to be elucidated.(J Epidemiol Community Health 1998;52:707-715)To be able to explain the behaviour of the incidence, mortality and morbidity of cardiovascular diseases (CVD), it is necessary to know the distribution and frequency of determining factors.CVD, particularly ischaemic coronary diseases (ICD) continue to be the main cause of death in Spain. In 1993, ICD represented a total of 20 785 deaths in men (11.6% of overall mortality) and 15 280 in women (9.6%). 1 Furthermore, ICD produce high morbidity in Spain: the cumulated incidence rate of acute myocardial infarction (AMI) in 1990-1992 per 100 000 inhabitants and year, standardised for age, in the 25-74 age group was 207.5 in men and 48.5 in women.2 Estimations of the prevalence of classic cardiovascular risk factors (CRF) have been made in Spain in population samples from various communities [3][4][5] and groups of workers.6 These studies, despite being well designed and conducted, diVer in the measurement methods used, which jeopardises their comparability. Moreover, studies in populations whose ICD incidence is known 2 and can be put i...

Objectives: To assess the effect of two similar olive oils, but with differences in their phenolic compounds (powerful antioxidant compounds), on inflammatory markers in stable coronary heart disease patients. Design: Placebo-controlled, crossover, randomized trial. Setting: Cardiology Department of Hospital del Mar and Institut Municipal d'Investigació Mèdica (Barcelona).Subjects: Twenty-eight stable coronary heart disease patients. Interventions: A raw daily dose of 50 ml of virgin and refined olive oil (ROO) was sequentially administered over two periods of 3-weeks, preceded by 2-week washout periods in which ROO was used. Results: Interleukin-6 (Po0.002) and C-reactive protein (P ¼ 0.024) decreased after virgin olive oil intervention. No changes were observed in soluble intercellular and vascular adhesion molecules, glucose and lipid profile. Conclusions: Consumption of virgin olive oil, could provide beneficial effects in stable coronary heart disease patients as an additional intervention to the pharmacological treatment.

The relation between dietary magnesium intake and cardiovascular disease (CVD) or mortality was evaluated in several prospective studies, but few of them have assessed the risk of all-cause mortality, which has never been evaluated in Mediterranean adults at high cardiovascular risk. The aim of this study was to assess the association between magnesium intake and CVD and mortality risk in a Mediterranean population at high cardiovascular risk with high average magnesium intake. The present study included 7216 men and women aged 55-80 y from the PREDIMED (Prevención con Dieta Mediterránea) study, a randomized clinical trial. Participants were assigned to 1 of 2 Mediterranean diets (supplemented with nuts or olive oil) or to a control diet (advice on a low-fat diet). Mortality was ascertained by linkage to the National Death Index and medical records. We fitted multivariable-adjusted Cox regressions to assess associations between baseline energy-adjusted tertiles of magnesium intake and relative risk of CVD and mortality. Multivariable analyses with generalized estimating equation models were used to assess the associations between yearly repeated measurements of magnesium intake and mortality. After a median follow-up of 4.8 y, 323 total deaths, 81 cardiovascular deaths, 130 cancer deaths, and 277 cardiovascular events occurred. Energy-adjusted baseline magnesium intake was inversely associated with cardiovascular, cancer, and all-cause mortality. Compared with lower consumers, individuals in the highest tertile of magnesium intake had a 34% reduction in mortality risk (HR: 0.66; 95% CI: 0.45, 0.95; P < 0.01). Dietary magnesium intake was inversely associated with mortality risk in Mediterranean individuals at high risk of CVD. This trial was registered at controlled-trials.com as ISRCTN35739639.