Population setting

This analysis was designed to compare the prevalence of cardiovascular risk factors in individuals with stable CHD living in two regions of South-West Europe: France and Spain. In France, participants were recruited as part of the Génétique et Environnement en Europe du Sud (GENES) study, a case-control study designed to assess the role of gene–environment interactions in the occurrence of CHD. Participants were men living in the Toulouse area (Haute-Garonne, South-West France, bordering on Spain), a region of 1.1 million inhabitants (540,000 men). Participants were included from 2001 to 2004. For the present analysis, only cases with a history of acute myocardial infarction were taken into account. Eligible participants were French male CHD patients, aged 45–74 years, living in the area of Toulouse and hospitalized in the Toulouse University Hospital for follow-up of stable CHD. Prior acute myocardial infarction had to be documented in the medical file of the patient and be determined from evidence of new pathological Q-waves on electrocardiogram, imaging evidence of healed acute myocardial infarction or evidence of a region of loss of viable myocardium that was thinned and failed to contract, in the absence of a non-ischaemic cause. Patients with confirmed acute myocardial infarction, electrocardiogram changes or rise in cardiac enzymes (> 1.5 times the upper limit) in the past 2 months, were excluded.

In Spain, the Registre Gironi del Cor Project (REGICOR) records all acute myocardial infarctions occurring in local inhabitants in six counties in Gerona. This province is located in North-East Spain, bordering on France, with a reference population of approximately 600,000 subjects. The registry process is done prospectively, and encompasses those patients admitted to the only referral hospital in the area. In order to be eligible, subjects have to be clinically diagnosed with acute myocardial infarction. Once identified, patients are classified according to the MONItoring of trends and determinants in CArdiovascular diseases (MONICA) project algorithm, which takes into account type of symptoms, electrocardiogram findings and enzymes . Selected patients were part of the definite non-fatal acute myocardial infarction group, defined as: definite electrocardiogram; or typical, atypical or inadequately described symptoms, together with probable electrocardiogram and abnormal enzymes; or typical symptoms and abnormal enzymes with ischaemic or non-codeable electrocardiogram or electrocardiogram not available . The inclusion period lasted between 1995 and 2004, although 75% of patients were recruited after 2001. A 6-month follow-up was done to measure blood lipid concentrations in patients with stable status.

In summary, men aged 45–74 years, with stable CHD, who reported a history of acute myocardial infarction were selected in both studies for the purpose of our analysis. The sample size (420 and 562 individuals in France and Spain, respectively), allowed us to detect differences between centres in the prevalence of cardiovascular risk factors of greater than 10 percentage-points, with a statistical power of at least 87.5%. Authorization from the local ethics committees was obtained in accordance with the French and Spanish laws and the Declaration of Helsinki. All participants were informed about the aim of the study and informed consent was signed by each subject.

Questionnaires

Age and socioeconomic variables were collected through standardized interviews. Smoking status was classified as smokers (current smokers or smokers who had quit for < 1 year), former smokers (those who had quit for > 1 year) and non-smokers. All medications taken were also recorded. Antiplatelet agents, beta-blockers, nitrates, calcium inhibitors, ACE inhibitors, diuretics, ARA II and lipid-lowering treatments were taken into account for the purposes of the study. In the REGICOR project, information on the last two drugs was only available from 2001.

Clinical measurements

Examinations were performed by a team of trained nurses, physicians and interviewers, who used equivalent standard questionnaires and measurement methods in both surveys . Anthropometrical measurements, including height and body weight were taken according to standardized procedures. BMI was determined as weight divided by height squared (kg/m ² ). Participants were classified into three groups according to BMI: normal weight, BMI < 25 kg/m ² ; overweight, BMI ≥ 25 and < 30; obese, BMI ≥ 30. Blood pressure was measured with a periodically calibrated mercury sphygmomanometer in Spain and an automatic sphygmomanometer (OMRON 705 CP) in France. A cuff adapted to the upper arm perimeter was selected for each participant. Measurements were performed after at least a 5-minute rest. Two measurements were taken and the lower value was recorded for the analysis. The cut-off points to define hypertension followed the criteria proposed in the Second Joint Task Force of European and Other Societies on Coronary Heart Disease Prevention in Clinical Practice and in the 2000 recommendations from the French Health Product Safety Agency . These guidelines were chosen as they were in current use in Spain and France when the studies were carried out. The guidelines recommended identical goals and methods for cardiovascular prevention, except regarding the target goal for cholesterol, which was lower in the European guidelines than in the French guidelines, as described in the next paragraph. The following definitions were used for hypertension and its treatment and control: history of hypertension (when participants reported a previous diagnosis or treatment for hypertension); real hypertension (history of hypertension or systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); treated hypertension (patients with a history of hypertension on drug treatment); controlled hypertension (systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg among treated patients). Reference values were systolic blood pressure < 130 mmHg and diastolic blood pressure < 80 mmHg for diabetic patients.

Blood sample collection and biological analyses

In both centres, blood was withdrawn after a 10–14-hour fast, with less than 60 seconds duration, at least 2 months after acute myocardial infarction (6 months in Spain). Serum sample aliquots were stored at −80 °C. Briefly, total cholesterol, glucose and triglyceride concentrations were determined enzymatically. HDL cholesterol was measured as cholesterol after precipitation of apoprotein B-containing lipoproteins with phosphotungstic-Mg ⁺⁺ . LDL cholesterol was calculated in both centres by the Friedewald equation whenever triglycerides were less than 3.4 mmol/L (389 and 544 individuals in France and Spain, respectively). Biological measurements were performed in a core laboratory in Barcelona for Spanish participants and in a core laboratory in the Toulouse University Hospital for French subjects . The cut-off points to define dyslipidaemia followed the criteria used in the Second Joint Task Force of European and Other Societies on Coronary Heart Disease Prevention in Clinical Practice (LDL cholesterol ≥ 3.0 mmol/L or HDL cholesterol ≤ 1.0 mmol/L) in Spain , and the 2000 recommendations from the French Health Product Safety Agency (LDL cholesterol ≥ 3.4 mmol/L or HDL cholesterol ≤ 1.0 mmol/L) in France .

Glucose metabolism disturbances were classified as follows: history of diabetes (participants already diagnosed by a physician); impaired fasting glycaemia (fasting glycaemia ranging from 6.1–6.9 mmol/L in participants not previously diagnosed with diabetes); real diabetes (participants with a history of diabetes or with fasting glycaemia ≥ 7 mmol/L); treated diabetes (patients with a history of diabetes under drug treatment).

Statistical analyses

Initially, the analyses were performed on the whole sample, then age-stratified analyses were done (45–59 years; 60–74 years). Continuous variables are summarized as means and standard deviations, and categorical variables are presented as proportions. Student’s t test was used to compare means of continuous variables. A logarithmic transformation was done to compute the p -value for variables whose distribution departed from normal (i.e., glycaemia and triglycerides). The χ ² -test was used to compare proportions. Statistical analysis was done with STATA software, version 9.2 (Stata Corp., College Station, TX, USA).