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Were to determine whether plasma atrial natriuretic peptide (ANP) is increased in patients with systemic sclerosis (SScl) and to evaluate its relation to cardiac dimensions and function.Using radio-immunoassay, plasma ANP was determined in 30 patients with SScl and 48 age and sex matched controls. The plasma ANP level was related to cardiac structure and function as determined by two-dimensional echocardiography (2-D echo).Plasma ANP was markedly elevated among patients as compared to controls (239,4 +/- 59 vs 178.2 +/- 36 pmpl/l, p0.0005). The left atrial long-axis and area were increased, and ANP was directly related to both measurements (r = 0.27, p0.05 and r = 0.40, p0.005, respectively). Plasma ANP was also related to the increased right atrial long-axis (r = 0.27, p0.05). The ANP level was not related to LV systolic function as estimated by ejection fraction, fractional area change and end-systolic wall stress, neither did these measures differ between patients and controls. However, there was an inverse correlation between ANP level and stroke volume (r = -0.35, p0.05), which was lower among the patients (p0.005). ANP displayed also an inverse relation to LV long axis diameter (r = -0.37, p0.005) and area (r = -0.42, p0.005) as well as to LV end-diastolic volume (r = -0.42, p0.005). Various measurements indicated LV hypertrophy among the SScl patients in spite of a small LV cavity. ANP was directly related to measures of LV hypertrophy, as interventricular septum thickness (r = 0.44, p0.005), LV posterior wall thickness (r = 0.34, p0.05), the wall thickness to cavity dimension ratio (r = 0.36, p0.05), and LV myocardial area (r = 0.36, p0.05). There was no relationship between ANP concentration and heart rate, blood pressure or total peripheral resistance.These results suggest that the ANP production is not reduced in SScl. Rather, circulating ANP is elevated in relation to the degree of LV hypertrophy. This implies that ANP may be useful for the identification of cardiac involvement in patients with SScl.