American Heart Journal
Volume 150, Issue 1 , Page e1, July 2005

Angiotensin I–converting enzyme insertion/insertion genotype as a genetic risk factor for cardiovascular disease

  • Akiyoshi Ogimoto, MD

      Affiliations

    • Second Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
    • Corresponding Author InformationReprint requests: Akiyoshi Ogimoto, MD, The Second Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan.
    • ,
  • Mareomi Hamada, MD

      Affiliations

    • Second Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
    • ,
  • Tetsuro Miki, MD

      Affiliations

    • Department of Geriatric Medicine, Ehime University School of Medicine, Ehime, Japan
    • ,
  • Jitsuo Higaki, MD

      Affiliations

    • Second Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan

Received 9 September 2003; accepted 8 May 2004.

Article Outline

 

To the Editor:

We read with great interest the study by Chou et al1 in a recent issue of the Journal. The authors showed that patients with mitral valve prolapse syndrome (MVPS) have a higher frequency of angiotensin I–converting enzyme (ACE) insertion/insertion (I/I) genotype.

This study surprised and encouraged us because we reported that the I/I genotype of the ACE gene is a significant risk factor for atrial fibrillation2 and cardiovascular events3 in patients with hypertrophic cardiomyopathy (HCM).

The renin angiotensin system regulates sodium balance and intravascular volume and, in addition, interacts with other blood pressure control mechanisms including the sympathetic nervous system and baroreflexes.4 Because patients with HCM have small left ventricular cavity size because of hypertrophy, reduction of intravascular volume is related to hypotension. In addition, exercise hypotension due to inappropriate peripheral vasodilation is demonstrated in patients with HCM.5 Therefore, activating renin angiotensin system may be a protective means for maintaining intravascular volume and systemic circulation in these patients. In fact, ACE inhibition in patients with HCM is known to aggravate hemodynamics6 and lead to hypotension and excessive systolic emptying.7 Thomson et al8 suggested that hypotension during central volume unloading might provide an additional or alternative trigger for arrhythmia in some patients with HCM.

In patients with MVPS, the reduction of left ventricular volume, such as a reduced venous return, tachycardia, or an augmentation of myocardial contractility, results in earlier occurrences of prolapse during systole. In addition, dehydration and administration of nitroglycerin deteriorate systemic circulation in patients with MVPS, which are similar to HCM.

Plasma ACE activity is significantly higher in individuals with the D allele than in individuals with the I allele. Patients with the ACE I/I genotype can be thought to be in a circulatory ACE inhibitory state and have unstable systemic circulation because of comparatively reduced intravascular volume than the other patients. Although many studies have suggested that the D allele is a risk factor for many types of cardiovascular disease, there are few reports that the ACE I/I genotype is a risk factor for cardiovascular disease. In general, excessive volume overload is harmful in most types of cardiovascular disease. On the contrary, however, it may actually be beneficial to patients with MVPS and HCM. Therefore, it may be acceptable that patients with MVPS have a higher frequency of the ACE I/I genotype as a genetic risk factor. Orthostatic hypotension and neurally mediated syncope should be investigated about the association with ACE gene polymorphism.

Back to Article Outline

References 

  1. Chou HT, Chen YT, Shi YR, et al. Association between angiotensin I–converting enzyme gene insertion/deletion polymorphism and mitral valve prolapse syndrome. Am Heart J. 2003;145:169–173
  2. Ogimoto A, Hamada M, Nakura J, et al. Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy. J Hum Genet. 2002;47:184–189
  3. Ogimoto A, Hamada M, Nakura J, et al. Relation between angiotensin-converting enzyme II genotype and cardiovascular events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2003;41(Suppl. A):146A
  4. Reid IA. Interactions between ANG II, sympathetic nervous system and baroreceptor reflexes in regulation of blood pressure. Am J Physiol. 1992;262:E763–E778
  5. Frenneaux MP, Counihan PJ, Caforio ALP, et al. Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy. Circulation. 1990;82:1995–2002
  6. Kyriakidis M, Triposkiadis F, Dernellis J, et al. Effects of cardiac versus circulatory angiotensin-converting enzyme inhibition on left ventricular diastolic function and coronary blood flow in hypertrophic obstructive cardiomyopathy. Circulation. 1998;97:1342–1347
  7. Topol EJ, Traill TA, Fortuin NJ. Hypertensive hypertrophic cardiomyopathy of the elderly. N Engl J Med. 1985;312:277–283
  8. Thomson HL, Morris-Thurgood J, Atherton J, et al. Reduced cardiopulmonary baroreflex sensitivity in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1998;31:1377–1382

PII: S0002-8703(05)00044-X

doi:10.1016/j.ahj.2004.05.063

American Heart Journal
Volume 150, Issue 1 , Page e1, July 2005

Article Tools