Synergistic effect of mitral expression of tissue inhibitor of metalloproteinase-2 with hypertension on the occurrence of mitral chordae tendinae rupture.
OBJECTIVE
We previously found the association between mitral chordae tendinae ruptures (MCTR) and hypertension. Tissue inhibitor of metalloproteinase-2 (TIMP2), which expresses differently under pressure loads, could trigger a signal cascade instigating cardiac fibrosis, possibly predisposing to MCTR. We aimed to elucidate the relationship between the TIMP2 and hypertension and the effect they may have on the occurrence of MCTR.


METHODS
Using a cross-sectional study in a tertiary medical center in Taiwan, we enrolled 186 patients who had received mitral valve replacements and classified them into two groups: 64 (34%) with MCTR and 122 (66%) without MCTR. Expression of mitral TIMP2 was assessed on a semiquantitative scale (grade 0-3) by immunohistochemical staining using antibodies against TIMP2.


RESULTS
TIMP2 expression was significantly higher in MCTR patients (P < 0.001). Multiple logistic regression analysis showed four independent risk factors: TIMP2 [odds ratio (OR) = 1.82, 95% confidence interval (CI) = 1.18-2.81, P = 0.007], hypertension (OR = 2.40, CI = 1.08-5.34, P = 0.032), rheumatic heart disease (OR = 0.18, CI = 0.05-0.70, P = 0.014), and left ventricular end-diastolic dimension (OR = 1.10, CI = 1.05-1.15, P < 0.001). Among nonhypertensive patients, the higher expression of TIMP2 (grade 2 and 3 vs. 0 and 1) was associated with a 3.27-fold risk. However, hypertensive patients with higher TIMP2 expression had a significantly 10-fold higher risk (P < 0.001 for interaction).


CONCLUSIONS
Mitral TIMP2 expression is higher in patients with MCTR and there is a synergistic effect of mitral TIMP2 staining with hypertension on the occurrence of MCTR.
Lin
Tsung-Hsien
TH
Department of Internal Medicine, Division of Cardiology, Kaohsiung Medical University Hospital, Taiwan, ROC.
Yang
Sheau-Fang
SF
Chiu
Chaw-Chi
CC
Lee
Ya-Ting
YT
Su
Ho-Ming
HM
Voon
Wen-Chol
WC
Lai
Wen-Ter
WT
Sheu
Sheng-Hsiung
SH
D000328:Adult; D000368:Aged; D002815:Chordae Tendineae / Q000201:enzymology / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006341:Heart Rupture / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000201:enzymology / Q000473:pathology; D008944:Mitral Valve Insufficiency / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D012214:Rheumatic Heart Disease / Q000453:epidemiology; D012307:Risk Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology
D019716:Tissue Inhibitor of Metalloproteinase-2