Increased Serum Concentrations of Procollagen Peptides in Essential Hypertension

Dı́ez, Javier; Laviades, C; Mayor, Gaspar; Gil, Marı́a J.; Monreal, Ignacío

doi:10.1161/01.cir.91.5.1450

Cited by 199 publications

(148 citation statements)

References 47 publications

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“…These findings are in agreement with previously published data. 25,26 We demonstrated a significant increase in TIMP-1 in the hypertensive cohort taken as a whole. However, only patients with echocardiographic evidence of diastolic dysfunction were found to have a significant elevation in plasma TIMP-1.…”

Section: Lindsay Et Al Timp-1: a Marker Of Fibrosis In Hypertensionmentioning

confidence: 70%

Timp-1

2002

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Abstract-This study was designed to document noninvasively the pathological mechanisms responsible for myocardial fibrosis and to assess the clinical utility of plasma markers of collagen synthesis and degradation as screening tools for the assessment of fibrosis in hypertension. We studied 100 never-treated hypertensive patients and 50 normal subjects. Echocardiographic assessment was made of left ventricular (LV) mass and diastolic filling using measurement of E:A ratio, E wave deceleration time (E dec), and isovolumic relaxation time (IVRT).

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Section: Lindsay Et Al Timp-1: a Marker Of Fibrosis In Hypertensionmentioning

confidence: 70%

Timp-1

2002

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“…20 The interassay and intra-assay variations for determining PIP were 7% and 3%, respectively. The sensitivity (lower detection limit) was 1.20 g PIP/L.…”

Section: Biochemical Determinationsmentioning

confidence: 95%

Losartan-Dependent Regression of Myocardial Fibrosis Is Associated With Reduction of Left Ventricular Chamber Stiffness in Hypertensive Patients

et al. 2002

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Background — This study was designed to investigate whether myocardial collagen content is related to myocardial stiffness in patients with essential hypertension. Methods and Results — The study was performed in 34 patients with hypertensive heart disease. Nineteen of these patients were also evaluated after 12 months of treatment with losartan. Transvenous endomyocardial biopsies of the interventricular septum were performed to quantify collagen volume fraction (CVF). Left ventricular (LV) chamber stiffness (K LV ) was determined from the deceleration time of the early mitral filling wave as measured by Doppler echocardiography. Histological analysis at baseline revealed the presence of 2 subgroups of patients: 8 with severe fibrosis and 26 with nonsevere fibrosis. Values of CVF and K LV were significantly higher in the 2 subgroups of hypertensives than in normotensives. In addition, compared with patients with nonsevere fibrosis, patients with severe fibrosis exhibited significantly increased values of CVF and K LV . After treatment, CVF and K LV decreased significantly in patients with severe fibrosis (n=7). None of these parameters changed significantly after treatment in patients with nonsevere fibrosis (n=12). CVF was directly correlated with K LV ( r =0.415, P <0.02) in all hypertensives. Conclusions — These findings show a strong association between myocardial collagen content and LV chamber stiffness in patients with essential hypertension. Our results also suggest that the ability of losartan to induce regression of severe myocardial fibrosis is associated with diminution of myocardial stiffness in hypertensive patients.

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“…Serum PIP was determined by radioimmunoassay according to a method previously described. 9 The interassay and intra-assay variations for determining PIP were 7% and 3%, respectively. The sensitivity (lower detection limit) was 1.20 g/L.…”

Section: Determination Of Pipmentioning

confidence: 95%

Ultrasonic Backscatter and Serum Marker of Cardiac Fibrosis in Hypertensives

et al. 2002

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Abstract-Elevations in the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP) Ͼ127 g/L have been found to predict severe myocardial fibrosis in hypertensive patients. This study was designed to assess whether ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the severity of myocardial fibrosis as estimated by serum PIP. Thirty-four subjects were included in the study. Serum PIP was measured by specific radio immunoanalysis. Backscatter cyclic variation and maximal intensity were measured in 6 regions throughout the left ventricle. The subjects were divided into 3 groups: 14 normotensives with PIP Ͻ127 g/L (group 1), 12 hypertensives with PIP Ͻ127 g/L (group 2), and 8 hypertensives with PIP Ͼ127 g/L (group 3). A n exaggerated accumulation of fibrillar collagens type I and type III occurs throughout the free wall and interventricular septum of animals 1,2 and humans 3,4 with primary arterial hypertension and left ventricular hypertrophy (LVH). A rise in collagen content has been shown to raise myocardial stiffness and promote abnormalities of cardiac function, electrical activity, and intramyocardial perfusion. 5 We have used serological markers of collagen turnover to address myocardial fibrosis of rats with spontaneous hypertension (SHR) 6 -8 and patients with essential hypertension 9 -12 and LVH. Serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, were higher in each setting of hypertensive heart disease, and there was a direct correlation between histological evidence and quantity of myocardial fibrosis and serum PIP concentration in SHR and hypertensive patients. Furthermore, in a recent study 12 we showed that hypertensives with serum concentrations of PIP Ͼ127 g/L have an almost 5-fold higher probability of presenting with histologically proven severe myocardial fibrosis than do hypertensives with serum PIP below this value. Thus, this cutoff value of PIP can be used to separate hypertensives likely presenting with severe myocardial fibrosis from subjects with nonsevere fibrosis. 13 Quantitative characterization of myocardial texture by analysis of ultrasonic reflectivity has been experimentally 14 -17 and clinically 18,19 shown to correlate with the collagen content of the myocardial tissue. We thus have hypothesized that PIP serum concentrations above 127 g/L should be associated with alterations in myocardial ultrasonic reflectivity detected by backscatter analysis. To test our hypothesis, maximal intensity (MI) and cyclic variation (CV) of backscatter signal were analyzed in normotensive subjects and hypertensive patients classified according to their serum concentrations of PIP. Methods SubjectsThe study population consisted of 34 subjects (27 men and 7 women, mean age 52 years, range 42 to 68 years) who were referred to our unit for routine cardiac evaluation. Twenty subjects presented elevated systolic blood pressure of Ͼ139 mm Hg and diastolic blood...

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Increased Serum Concentrations of Procollagen Peptides in Essential Hypertension

Cited by 199 publications

References 47 publications

Timp-1

Timp-1

Losartan-Dependent Regression of Myocardial Fibrosis Is Associated With Reduction of Left Ventricular Chamber Stiffness in Hypertensive Patients

Ultrasonic Backscatter and Serum Marker of Cardiac Fibrosis in Hypertensives

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