C reactive protein and its determinants in healthy men and women from European regions at different risk of coronary disease: the IMMIDIET Project.

AIM: Differences in C-reactive protein (CRP) levels and its determinants in three European populations at different risk of coronary artery disease (CAD) were studied. METHODS: Subjects were recruited randomly in Limburg (Belgium), Abruzzo (Italy) and south-west (SW) London (England). RESULTS: Ten-year risk of fatal coronary events (estimated using risk equations provided by the SCORE Project) was lower both in men and women from Abruzzo, intermediate in people from Limburg and higher in subjects from SW London. Within each country, high sensitivity (hs)-CRP levels were higher in the high-risk class in men but not in women. Men from Abruzzo had higher hs-CRP levels than those from Limburg and SW London. Women always had higher hs-CRP levels than men. The strongest hs-CRP determinant was body mass index (BMI, R(2) = 0.14) in women and waist circumference (WC, R(2) = 0.046) in men. The highest hs-CRP levels were observed in subjects with both high BMI and high WC. Metabolic syndrome was associated with high levels of CRP both in men and women, even after adjustment for confounders. DISCUSSION: Difference in CRP levels cannot explain the European gradient of CVD risk, although CRP levels are associated with the calculated SCORE risk of fatal coronary events within each country.

Dietary habit profile in European communities with different risk of myocardial infarction: the impact of migration as a model of gene-environment interaction. The IMMIDIET Study.

The risk of myocardial infarction (MI) is lower in southern than in northern European countries. The lower rate of MI in the Mediterranean regions of Europe suggested a potential role of the traditional Mediterranean diet in the prevention of MI. Unfortunately, in the last 20 years, a tendency to adopt Westernised food habits even in southern regions of Europe is reflected by an increase in the prevalence of obesity. Therefore the impact of diet on MI risk profile among European populations needs to be reconsidered. Genetic risk factors have also been implicated in the development of MI. Genes, indeed, continuously interact with environmental factors in determining the pathogenesis of MI. The aims of the IMMIDIET study are to evaluate: 1. The present dietary habits and the risk profile of three European communities at different risk of MI; 2. The impact of migration on risk factors for MI. Dietary habits and genetic polymorphisms will be evaluated in an Italian, Belgian and British population sample. The historical Italian migration to Belgium and the integration through mixed marriage will be considered as a model of gene-environment interaction. As an index of MI risk profile, factors that are most likely under the combined influence of both dietary and genetic determinants will be investigated.

Pharmacogenetics: a molecular sophistication or a new clinical tool for cardiologists?

The study of genetic risk factors for multifactorial diseases is attracting increasing interest. In particular interest has been focused on the interaction between genetic polymorphisms and environmental factors in determining the risk of disease. Among environmental factors therapeutic approaches should be considered. Therapeutic responses to a given drug, failure of drug efficacy, interindividual variability in side effects and toxicity of drugs could be at least partially accounted for by genetic polymorphisms. This paper summarizes the presently available applications of genetic concepts to some drugs commonly used in patients with cardiovascular disease. Statins and probucol fail to lower cholesterol levels in carriers of specific polymorphisms. The progression of cardiovascular disease is decreased by pravastatin only when certain polymorphisms are present. Induction problems and bleeding complications of warfarin occur in subgroups of populations carrying specific genetic variants of key enzymes in the drug metabolism. A new interpretation of the results of a thrombosis prevention trial will be given in the light of a genetic approach to pharmacology; indeed, prevention and treatment of thrombotic disease could be better focused on the basis of this knowledge. Future clinical trials and cost-effectiveness evaluation of drugs should be conducted taking these gene-drug interactions into account.