Angiotensin-converting enzyme genotype predicts valve damage in acute rheumatic fever

The genetic basis for host susceptibility to subsequent valve damage and scarring is not well defined in patients with a history of acute rheumatic fever (ARF). A high angiotensin-converting enzyme (ACE) activity has been demonstrated in valve tissue; hence, the study aim was to determine whether the ACE-DD genotype was a predisposing factor to heart valve damage after ARF attack.

A total of 165 patients diagnosed previously (16 +/- 5 years ago) with ARF was evaluated. Diagnoses were conducted according to Jones' criteria, and all received similar treatment and remain on regular penicillin prophylaxis. The ACE genotype was determined using polymerase chain reaction methods.

Echocardiography showed that 39 patients (11 males, 28 females; mean age 25 +/- 6 years) had completely normal valves, and 126 patients (38 males, 88 females; mean age 21 +/- 6 years) had valve disease. The mitral valve was involved in 93% of patients (stenosis 86%, regurgitation 69%), and the aortic valve in 50% (stenosis 19%, regurgitation 48%). The ACE-DD genotype is associated with a significantly greater risk of valve involvement (risk ratio 2.7, 95% CI 1.15-6.5, p = 0.02). The distribution of genotypes was similar between aortic and mitral valve involvement.

In patients with acute rheumatic fever the ACE-DD genotype is associated with an increased risk of subsequent heart valve damage.