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Angiotensin converting enzyme gene polymorphism and cardiovascular morbidity and mortality: the Rotterdam Study
  1. F A Sayed-Tabatabaei,
  2. A F C Schut,
  3. A Arias Vásquez,
  4. A M Bertoli-Avella,
  5. A Hofman,
  6. J C M Witteman,
  7. C M van Duijn
  1. Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
  1. Correspondence to:
 F A Sayed-Tabatabaei
 Department of Epidemiology and Biostatistics, Erasmus Medical Center, Postbus 1738, 3000 DR Rotterdam, The Netherlands;


Background: Findings on the association between the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene and cardiovascular morbidity and mortality have been inconsistent. Considering the possible interaction between this polymorphism and smoking, we evaluated the association between ACE I/D polymorphism and myocardial infarction (MI), mortality due to coronary heart disease (CHD), and cardiovascular disease (CVD).

Methods: The study was performed within the Rotterdam Study, a population based cohort study. The ACE I/D polymorphism was determined for 6714 participants and smoking status recorded at baseline. Fatal and non-fatal MIs and mortality events were regularly recorded. Cox proportional hazard analysis was performed separately for current smokers and non-smokers. We used age as the follow up time, presenting age specific survivals.

Results: During follow up, 248 MIs and 301 and 482 deaths, respectively, due to CHD and CVD occurred. There were no significant differences between the genotypes as regards MI incidence. Among smokers, there was an increased risk of CHD and CVD mortality in carriers of the DD genotype compared to the II genotype, which diminished at later ages (p<0.01 for gene-age interaction). Subgroup analysis in a younger and older group (based on the median age of 68.2 years) showed a significantly increased risk of CVD mortality in the younger group (hazard ratio = 5.19; 95% confidence interval: 1.15 to 23.42).

Conclusions: This study showed that the ACE I/D polymorphism is not a strong risk factor for MI but its interaction with smoking might play a role in cardiovascular mortality especially at younger ages.

  • ACE, angiotensin I-converting enzyme
  • CHD, coronary heart disease
  • CVD, cardiovascular disease
  • I/D, insertion/deletion
  • IMT, intima media thickness
  • MI, myocardial infarction
  • angiotensin
  • genes
  • morbidity
  • mortality
  • smoking

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  • This study was supported by the Netherlands Organization for Scientific Research (NWO), grant 904-61-196. The study utilised facilities funded by the Centre for Medical Systems Biology. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.

  • Competing interests: none declared