Hypothesis: an angiotensin converting enzyme genotype, present in one in three caucasians, is associated with increased mortality rate.

1. This review argues that the deletion (D) allele of an insertion (I)/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene is a marker for a variant associated with increased ACE expression, as well as myocardial infarction (MI) and other life-threatening conditions. 2. By examination of I/D frequency in different age groups of individuals having well-known risk factors, it appears that homozygosity for the D allele may be associated with an increased risk of premature death in subjects at high-risk of cardiovascular events. For the risk factor hypertension, the odds ratio for DD vs II in patients aged > or = 60 years was 6.6. 3. Besides in MI itself, the DD genotype appears to be also more prevalent in MI patients who develop restenosis several months after balloon angioplasty, patients with various forms of heart failure, those with ventricular hypertrophy and diabetic patients who develop nephropathy. 4. Particular genotypes of other components of the renin-angiotensin system may add to the risk conferred by the ACE DD genotype. 5. Emerging evidence therefore suggests that the ACE genotype may eventually be placed on the list of common, well-known risk factors for fatal cardiovascular events.