The Stockholm Heart Epidemiology Program (SHEEP)

The SHEEP is a population based case-control study of risk factors for first episode of acute myocardial infarction (MI). The study base comprised all Swedish citizens resident in the Stockholm county 1992-1994 who were 45-70 years of age and were free of previous clinically diagnosed myocardial infarction.

MI cases were identified using three different sources: 1) coronary units and internal medicine wards for acute care in all Stockholm hospitals; 2) the National Patient Register; and 3) death certificates. The total number of cases identified amounts to 2246 (1485 male and 761 female). Out of those, 1643 survived at least 28 days after the MI and were considered non-fatal cases.

Controls were randomly recruited from the study base continuously over time within 2 days of the case occurrence and matched to cases on age (5-years interval), sex and hospital catchment area using computerized registers of the population of Stockholm. Five control candidates were sampled simultaneously to be able to replace potential non-respondent controls. Occasionally, because of late response of the initial control, both the first and alternative controls were considered, resulting in the inclusion of more controls than cases. In total, 3206 controls were included.

Postal questionnaires covering a wide range of exposure areas including occupational exposures, life style factors, social factors and health related factors were distributed to the participants. Incomplete questionnaire information was completed through telephone interviews. For fatal cases, a close relative was asked to fill in the questionnaire. Female cases and their controls answered an additional questionnaire on the use of menopausal hormone therapy and oral contraceptives. Clinical investigations were performed at least three months after myocardial infarction of cases and their matched controls. The investigations included blood samplings under fasting conditions with collection of whole blood for DNA extraction, serum and plasma. Serum, plasma (citrated and EDTA) and whole blood are frozen in -80°C. DNA has been extracted and amplified.

The SHEEP database is primarily used to evaluate exposures and risk factors for first time MI and factors influencing short- and long-term prognosis after MI. Interest is also directed at analyzing the importance of interactions between various risk factors including gene-environmental interactions. Mechanisms of potential significance for atherosclerosis are studied as well as novel genes that might generate development of new targets for treatment. Emphasis is put on further exploring the functional relevance of the genetic associations identified including the search for rare alleles through deep sequencing. Data from over 200,000 SNPs in a cardiometabolic chip is available.

Exposure information based on both the questionnaire and biological data from the health examination is available for 78% of the male and 67% of the female non-fatal cases; the corresponding figures for their controls are 68% and 64%.

Financing

• Swedish Research Council
• Heart & Lung Foundation
• Stockholm County Council (ALF)
• the Cardiovascular Programme at Karolinska Institutet
• European Union grant

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