The relation between serum concentrations of procollagen peptides and cardiac changes-evaluation by integrated backscatter and thallium-201 SPECT in hypertensive patients
越來越多的研究顯示心肌纖維化在高血壓心臟變化中扮演了相當重要的角色。利用免疫組織化學呈相法顯示在高血壓心臟病的患者，其心臟間質及冠狀動脈週圍有大量的第一類及第三類纖維膠原沉積。大量的心臟纖維化會導致心室收縮功能異常、冠狀動脈血流異常、及心律不整。在各種人體有關心臟纖維化的病理研究中發現:心肌細胞的超音波反射度與膠原堆積的量有相當程度的關聯性。因此對研究心肌纖維化而言; 加成性超音波逆行散射(週期變化與波幅大小的改變)便成為一種優良的非侵襲性工具。另一方面，膠原纖維原分解的過程中會釋放一些物質如第一類膠原纖維原碳基端分解物(PIP)、第三類膠原纖維原胺基端分解物(PIIIP)至血清中。據研究顯示，這些血清中的膠原纖維分解物與心肌纖維化有關。在肝功能正常的前提下，這些血清中的膠原纖維分解物與組織中膠原纖維製造有量化性的相關。因此我們設計這個研究；將病患分成三組: A 組為正常對照組B 組高血壓病患其血中PIP<127ug/、C 組高血壓病患其血中PIP≧127ug/L。這個研究目的有(1) 比較這三組病患加成性超音波逆行散射(週期變化與波幅大小的改變)與血清中的膠原纖維
分解物(PIP 與PIIIP)之相關 (2) 鉈-201心肌造影與清中的膠原纖維分解物(PIP與PIIIP)之相關。共有21 名病患進入本研
究(每組各7 名)。左心室後壁的加成性超音波逆行散射波幅在C 組與A 及B 組病患有明顯差異(A 組 8.4±1.6 dB; B 組8.8± 2.0dB;C 組6.2 ± 0.8dB)。週期變化則無明顯變化。左心室後壁的加成性超音波逆行散射波幅大小改變之多變項線性回歸與PIP有明顯相關(p<0.05);但與PIIIP 無關。鉈-201 心肌造影與清中的PIIIP 有相關: 有可逆性灌流缺損有者較高之PIIIP(5.6 ±1.2 ug/L vs 4.5 ± 1.0 ug/L; p<0.05)；有固
定性心肌灌流缺損者亦有較高之PIIIP(6.7 ± 1.1 ug/L vs 4.8 ± 0.9 ug/L;p=0.001)。結論: 高血壓病患超音波逆行散
射波幅與膠原纖維分解物PIP 有明顯相關，但與PIIIP 無關。A growing body of evidence indicates that myocardial fibrosis is one of the key pathologic features of myocardial remodeling in hyperensive heart disease. An exaggerated accumulation of collagens type I and type III within the myocardial interstitium and surrounding intramural coronary arteries and arterioles has been evidenced immunohistologically in patients with hypertensive heart disease. Myocardial
fibrosis predisposes to ventricular dysfunction, diminished coronary reserve and ventricular arrhythmias, which, in turn, confer increased risk of adverse cardiovascular events to patients with hypertension. To determine the extent of collagen accumulation in tissue may be relevant in assessing the clinical outcome of
these patients and in designing strategies to
prevent its appearance or even to cause its
regression. Studies performed in human with
different pathologic conditions involving
myocardial fibrosis have shown a promising
correlation between echo-reflectivity and
histologically assessed collagen content.
Therefore, cyclic variation of in returning
ultrasound signal intensity (cyclic variation
of integrated backscatter) turns to be a
non-invasive tool for measurement of myocardial fibrosis. On the other hand, serum procollagen type I carboxy-terminal peptide (PIP) and procollagen type III amino terminal peptide (PIIIP) have been related to myocardial fibrosis. Serum PIP and PIIIP concentration can be considered as a useful marker of myocardial collagen type I and III synthesis in conditions of preserved liver function. Therefore, we classified the hypertensive patients into 3 groups. Group A served as control group; group B included hypertensive patients with PIP<127 ug/L; C included hypertensive patients with PIP ≧
127 ug/L. This prospective study was designed (1) to analyze the relation between myocardial integrated backscatter and serum markers (PIP and PIIIP) of myocardial fibrosis (2) to analyze the relation between myocardial thallium-201 imaging and serum markers (PIP and PIIIP) of myocardial fibrosis. Group C had the lowest amplitude of CVIBS at the left ventricular posterior wall [LVPW] (group A 8.4±1.6 dB; group B 8.8± 2.0 dB; group C 6.2 ± 0.8dB). There was no significant chages of phase among 3 groups. Multi-variate linear regression showed significant association between CVIBS and PIP rather than PIIIP (p<0.05). There was significant association between thallium-201 imaging between PIIIP rather than PIP. Patients with reversible or fixed perfusion defects had the higher levels of PIIIP than those without (5.6 ± 1.2 ug/L vs 4.5 ± 1.0 ug/L, p<0.05; 6.7 ± 1.1 ug/L vs 4.8 ± 0.9 ug/L; p=0.001). In conclusion: The CVIBS of LVPW is associated with PIP rather than with PIIIP
