Myocardial Collagen Cross-Linking Is Associated With Heart Failure Hospitalization in Patients With Hypertensive Heart Failure

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• 作者：Begoñ ; a Ló ; pez ; PhD^&lowast ; ; ^&dagger ; ; Susana Ravassa ; PhD^&lowast ; ; ^&dagger ; ; Arantxa Gonzá ; lez ; PhD^&lowast ; ; ^&dagger ; ; Elena Zubillaga ; MD ; PhD^&Dagger ; ; Claudia Bonavila ; MD^§ ; ; Magda Bergé ; s ; MD^§ ; ; Kattalin Echegaray ; MD^§ ; ; Javier Beaumont ; PhD^&lowast ; ; ^&dagger ; ; Marí ; a U. Moreno ; PhD^&lowast ; ; ^&dagger ; ; Gorka San José ; PhD^&lowast ; ; ^&dagger ; ; Mariano Larman ; MD ; PhD^§ ; ; Ramó ; n Querejeta ; MD ; PhD^§ ; ; Javier Dí ; ez ; MD ; PhD^&lowast ; ; ^&dagger ; ; ^‖ ; ^{jadimar@unav.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：biomarker ; cardiovascular death ; heart failure of hypertensive etiology ; myocardial fibrosis
• 刊名：Journal of the American College of Cardiology
• 出版年：2016
• 出版时间：26 January 2016
• 年：2016
• 卷：67
• 期：3
• 页码：251-260
• 全文大小：1207 K

文摘

Excessive myocardial collagen cross-linking (CCL) determines myocardial collagen’s resistance to degradation by matrix metalloproteinase (MMP)-1 and interstitial accumulation of collagen fibers with impairment of cardiac function.

Objectives

This study sought to investigate whether CCL and a newly identified biomarker of this alteration are associated with hospitalization for heart failure (HHF) or cardiovascular death in patients with HF and arterial hypertension in whom other comorbidities were excluded.

Methods

Endomyocardial biopsies and blood samples from 38 patients (invasive study), and blood samples from 203 patients (noninvasive study) were analyzed. Mean follow-ups were 7.74 ± 0.58 years and 4.72 ± 0.11 years, respectively. Myocardial CCL was calculated as the ratio between insoluble and soluble collagen. The ratio between the C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase-1 (CITP:MMP-1) was determined in blood samples.

Results

Invasive study: CCL was increased (p < 0.001) in patients compared with controls. Patients were categorized according to normal or high CCL values. Patients with high CCL exhibited higher risk for subsequent HHF (log-rank test p = 0.022), but not for cardiovascular death. CITP:MMP-1 was inversely associated with CCL (r = −0.460; p = 0.005) in all patients. Receiver operating characteristic curves rendered a CITP:MMP-1 cutoff ≤1.968 (80% sensitivity and 76% specificity) for predicting high CCL. Noninvasive study: Patients were categorized according to CITP:MMP-1 ratio values as normal ratio (>1.968) or low ratio (≤1.968). Patients with a low ratio exhibited higher risk for HHF (log-rank test p = 0.014), which remained significant after adjustment for relevant covariables (adjusted hazard ratio: 2.22; 95% CI: 1.37 to 3.59, p = 0.001). In addition, CITP:MMP-1–based categorization yielded significant integrated discrimination and net reclassification improvements (p = 0.003 and p = 0.009, respectively) for HHF over relevant risk factors. CITP:MMP-1 was not associated with the risk of cardiovascular death.

Conclusions

Excessive myocardial CCL is associated with HHF in hypertensive patients with HF. In this population, the serum CITP:MMP-1 ratio identifies patients with increased CCL and high risk of HHF.