OPERA (Oulu Project Elucidating Risk of Atherosclerosis) is a population-based, epidemiological case-control study addressing the risk factors and disease end-points of atherosclerotic cardiovascular diseases. The hypertensive cohort (cases) consisted of altogether 600 subjects (300 men and 300 women) living in the town Oulu, whose age on September 1, 1990 was between 40 and 59 years and who, according to the register of the Social Insurance Institution, were entitled to a special refund (higher reimbursement class) of hypertension medication endorsed later than August 1980. The subjects were randomly selected by the Social Insurance Institution in 1990. To ensure an adequate recruitment of younger subjects, the randomization was age-stratified, i.e. for each year of birth (from 1931 to 1950), 15 hypertensive men and 15 hypertensive women were selected. For each hypertensive subject, an age- and sex-matched control subject living in Oulu was randomly selected from the national health register (including all inhabitants), excluding subjects entitled to a special refund for hypertension medication. Altogether, the study population consisted of 1200 subjects. After the randomization, the criteria of the special refund for antihypertensive medication were slightly amended in April 1994. According to the criteria used in 1989, the Social Insurance Institution reimbursed 90% of the costs of the drug treatment for moderate or severe hypertension. To be eligible for the 90% refund, the hypertensive patient was to have a DBP level of 105 mmHg or more during a few months’ follow-up, unless the patient already showed signs of LVH or other target organ damage caused by hypertension (heart failure, CHD, cerebrovascular disease, renal insufficiency or hypertensive retinopathy) at presentation. In that case, the DBP limit was 100 mmHg. If the patient was young (men below 50 years, women below 40 years), had a family history of CVD or sudden death at an early age, had diabetes or severe hyperlipidemia or had a SBP above 180 mmHg (above 200 mmHg in subjects older than 50 years), he or she was eligible for the 90% refund even when her/his DBP level during the follow-up was 100–104 mmHg. In the case of diabetic or other nephropathy, the lower DBP limit (95 mmHg) was sufficient to entitle to reimbursement. The subjects treated by non-pharmacological regimens for mild hypertension were included in the control cohorts. This middle-aged population sample included a large proportion of subjects with high blood pressure previously undetected and untreated.
The selected subjects were recruited by an invitation letter to participate in the the study, and one reminder letter was sent when necessary. The letters were mailed by the Social Insurance Institution. The first invitations were mailed at the end of 1990.
The participating study subjects visited the research laboratory of the Department of Internal Medicine of the University of Oulu between January 1991 and March 1993, first the men (during 1991 and early 1992) and then the women. All the hypertensive subjects were investigated without prior discontinuation of drug therapy. Menopausal age was 48.6 years in hypertensive women and 48.4 years in control women (p = 0.8). All the subjects arrived at the laboratory in the morning after an overnight fast and were examined between 8 am. and 1 pm. At this visit, anthropometric measurements (weight, height, waist, hip), blood pressure measurements and standard ECG were performed. The OGTTs were performed immediately after fasting blood for other tests had been drawn. During the same visit, a standardized health questionnaire covering the past medical history, current and former medication use, physical activity, smoking habits, alcohol consumption and family history was administered by two specially trained study nurses. The details of the questionnaire were checked by the physician later during the same visit. Three trained physicians with special competence in internal medicine interviewed and examined all the study subjects. Finally, a chest X-ray was obtained in the Department of Diagnostic Radiology.
All the subjects voluntereed into the study, which was approved by the Ethical Committee of the University of Oulu.