Myocardial fibrosis in hypertensive patients and patients with coronary artery disease

• Main Authors: Yen-Hung Lin, 林彥宏
• Other Authors: Wen-Jone Chen
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/90634410433650773389

碩士 === 國立臺灣大學 === 臨床醫學研究所 === 93 === More and more studies reveal that myocardial fibrosis plays a very important role in hypertensive myocardium and ischemic myocardium. In immunohistochemical stain, large amount type I and type III collagen accumulate in the interstitial and perivascular space of extracelluar matrix in hypertensive myocardium. Myocardial fibrosis results in ventricular diastolic dysfunction, coronary flow disturbance, and arrhythmia. In various clinical and pathological studies relating myocardial fibrosis reveal that there is a significant association between echo reflection of myocardium and collagen amount. Cyclic variation of integrated backscatter (CVIBS) is an excellent, noninvasive tool to evaluate myocardial fibrosis. Procollagen propeptides, such as carboxy-terminal propeptide of procollagen type I, amino-terminal propeptide of procollagen type I, and amino-terminal propeptide of procollagen type III, are released to serum as by-products during collagen synthesis. In various studies, the procollagen propeptides are quantitatively related to myocardial fibrosis. So we design these two studies to evaluate myocardial fibrosis in hypertensive patients and patients with coronary artery disease (CAD). A total of 21 patients were enrolled into the first study and were divided in 3 groups according to presence of hypertension and serum carboxy-terminal propeptide of procollagen type I (PICP) concentration: 7 hypertensive patients with PICP≧127μg/l (group 1), 7 hypertensive patients with PICP<127μg/l (group 2), 7 normotensive subjects with PICP<127μg/l (group 3). In addition to PICP, serum amino-terminal propeptide of type III procollagen (PIIINP), stress thalium-201 scintigraphy and CVIBS were examined. Amplitudes of CVIBS and phase-compensated amplitudes of CVIBS at mid posterior segments were significantly lower in group 1 (p<0.05). Patients with reversible or fixed thallium-201 perfusion defects had higher PIIINP concentrations (p<0.05). Patients with fixed thallium-201 perfusion defects had lower phase-compensated amplitudes of CVIBS at mid antero-septal segment (p=0.002). In conclusions, decrease of myocardial phase-compensated amplitude accompanied with increase of serum PICP concentration may be indicative of the underlying fibrotic process of hypertensive myocardium. Decrease of this CVIBS parameter with increase of serum PIIINP implies concomitant myocardial ischemia. Although the collagen accumulation after myocardial infarction is well established, there is little known about the myocardial fibrosis in patients having CAD without myocardial infarction. The effect of reperfusion to myocardial fibrosis is not known. We design the second study to evaluate the myocardial fibrosis in patients with CAD and the effect of reperfusion therapy. A total of 46 patients (32 men and 14 woman; mean age 64 years) with chest pain and normal left ventricular contractility were enrolled into this study. Myocardial infarction was excluded by history and electrocardiograms. All patients received stress thallium-201 scintigraphy and analysis of the serum levels of the aminoterminal propeptide of type I procollagen (PINP) and PIIINP. Results: Nine patients had no perfusion defects in stress thallium-201 SPECT (group1). The other 37 patients with reversible perfusion defects received coronary angiography. There were 13 patients with patent coronary arteries (group2). In 24 patients with significant CAD (group 3), the patient numbers of 1-, 2-, and 3-vessel disease are 12, 6, and 6, respectively. In patients with thallium-201 perfusion defects, the number of diseased vessels was associated significantly with PIIINP (p=0.024) rather than PINP. Reperfusion therapy with percutaneous coronary intervention was performed in 28 vessels out of 22 patients. Serum PINP and PIIINP levels were followed after coronary intervention (mean 84 days) and revealed no significant change comparing with baseline level. In conclusions, serum PIIINP level is significantly associated with the severity of CAD in patients without myocardial infarction or hibernation. Short term follow-up fails to document the changes of serum PIIINP levels after reperfusion therapy. Cardiac diseases are the main causes of death and hospitalization in Taiwan. Hypertension and CAD are two of the most common causes. The studies associated with the mechanism of myocardial fibrosis in hypertensive and ischemic myocardium are primitive. We hope that we can open a new window for basic research of myocardial fibrosis.