Reduction of pneumonia risk by an angiotensin I-converting enzyme inhibitor in elderly Japanese inpatients according to insertion/deletion polymorphism of the angiotensin I-converting enzyme gene.
BACKGROUND
We have reported that use of angiotensin I-converting enzyme (ACE) inhibitor, which is a class of antihypertensive agent that induces cough, is an independent factor in reducing risk of pneumonia among elderly inpatients. Insertion/deletion (I/D) polymorphism of the ACE gene (ACE) has been associated with the risk of pneumonia in elderly individuals. However, the ability of ACE inhibitors to reduce pneumonia-related morbidity in individuals with the ACE polymorphism is unclear. Therefore we determined the association of ACE inhibitor use and ACE genotypes with reduction of pneumonia risk in the Japanese elderly population.


METHODS
We conducted a hospital-based, retrospective, case-control study to evaluate the effect of an ACE inhibitor and ACE polymorphism on incidence of pneumonia. Case subjects were pneumonia patients (N = 105) >or=65 years of age, during an 8-month period of a nonwinter season. Control subjects (n = 420) were elderly patients who were frequency matched to the case subjects by age (within +/- 2 years) and gender. Data were collected on medication with the ACE inhibitor temocapril and on known risk factors for pneumonia. The significances of differences for the risk factors were analyzed using univariate and multivariate comparisons of the case and control subjects.


RESULTS
After adjustment for potential confounders by multiple logistic regression analysis, the odds ratio (OR) estimates for pneumonia were 0.458 (95% confidential interval [CI]: 0.230 to 0.909, P = .026) for ACE inhibitor use. Conditional logistic regression analysis according to ACE genotypes revealed significant reduction of pneumonia risk by use of temocapril compared with that in nonhypertensive individuals (ie, the reference group) in those with ACE ID + II (OR: 0. 416, 95% CI: 0.177 to 0.976, P = .044), but not in those with ACE DD (OR: 0.706, 95% CI: 0.198 to 2.518, P = .592).


CONCLUSIONS
These results suggest that use of an ACE inhibitor is beneficial for reducing risk of pneumonia, particularly in individuals with the ACE genotypes ID + II.
Takahashi
Takashi
T
Department of General Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Morimoto
Shigeto
S
Okaishi
Kohya
K
Kanda
Tsugiyasu
T
Nakahashi
Takeshi
T
Okuro
Masashi
M
Murai
Hiroshi
H
Nishimura
Yukiharu
Y
Iwai
Kunimitsu
K
Matsumoto
Masayuki
M
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D015999:Multivariate Analysis; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011014:Pneumonia / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013841:Thiazepines / Q000627:therapeutic use; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D013841:Thiazepines; C055603:temocapril hydrochloride; D007703:Peptidyl-Dipeptidase A