(Circulation. 1995;91:1450-1456.)
© 1995 American Heart Association, Inc.
Articles |
Increased Serum Concentrations of Procollagen Peptides in Essential Hypertension
Relation to Cardiac Alterations
From the Department of Internal Medicine (J.D.), Center for Biomedical Research, School of Medicine, University of Navarra, Pamplona, and the Department of Medicine (J.D.), School of Medicine, University of Zaragoza, Zaragoza; the Division of Medicine (C.L., G.M.), San Jorge General Hospital, Huesca; and the Department of Clinical Biochemistry (M.J.G., I.M.), University Clinic, School of Medicine, University of Navarra, Pamplona, Spain.
Correspondence to Javier Díez, MD, PhD, Unidad de Fisiopatologia Vascular, Dpto de Medicina Interna, Centro de Investigaciones Biomédicas, Facultad de Medicina, C/ Irunlarrea s/n, 31080 Pamplona, Spain.
Background The serum concentrations of two procollagen-derived peptides, procollagen type III amino terminal peptide (PIIIP) and procollagen type I carboxy terminal peptide (PIP), have been proposed as useful markers of the tissue synthesis of collagen type III and type I, respectively. Therefore, this study was designed to evaluate fibrogenic activity in patients with essential hypertension by measuring serum PIIIP and PIP. Furthermore, since hypertensive heart disease is characterized by myocardial accumulation of collagen type III and type I, a second aim of the study was to assess whether some relation exists between the serum concentrations of PIIIP and PIP and several parameters of left ventricular anatomy and function in hypertensive patients.
Methods and Results The study was performed in 50 patients with never-treated essential hypertension and in 30 normotensive control subjects. Measurements were repeated in 43 hypertensive patients after 6 months of treatment with the angiotensin-converting enzyme inhibitor lisinopril. The serum concentrations of PIIIP and PIP were measured by specific radioimmunoassay. Two-dimensional, targeted M-mode and Doppler ultrasound recordings were obtained in every subject to determine several parameters of the left ventricle anatomy and function. Ambulatory ECG monitoring was performed in each patient, and the recorded ventricular arrhythmias were categorized according to Lown-Wolf classification. Baseline serum PIIIP and PIP were increased (P<.001) in hypertensive patients as compared with normotensive subjects. An inverse correlation was found between serum PIIIP and the ratio between maximal early transmitral flow velocity and maximal late transmitral flow velocity measured during diastole (r=-.3786, P<.01) in the group of hypertensive patients. Serum PIP was correlated directly with the left ventricular mass index (r=.3277, P<.05) in the group of hypertensive patients. Serum PIP concentrations increased in parallel with the increase in the grade of ventricular arrhythmias in the group of hypertensive patients. Treated patients attained normalization in blood pressure, amelioration of diastolic filling, regression of left ventricular mass index, and a diminution in the number of daily ventricular extrasystoles. In addition, serum PIIIP and PIP concentrations decreased significantly (P<.001) to normal values in patients treated with lisinopril.
Conclusions These findings suggest that tissue synthesis of collagen type III and type I is abnormally increased in essential hypertension and can be normalized by treatment with lisinopril. On the other hand, our results suggest that serum PIIIP and PIP are related to several anatomic and functional alterations of the hypertensive left ventricle. Serum procollagen peptide measurements may therefore provide indirect diagnostic information on the myocardial fibrosis associated with arterial hypertension.
Key Words: hypertension • hypertrophy • peptides
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