Abstract-Blood (or plasma) rheology is related to cardiovascular risk. Mechanisms of this association are unclear but may be partially related to impaired left ventricular (LV) function and increased central blood pressure (BP) during light activity. This study aimed to test these hypotheses. Twenty patients (14 men; aged 61Ϯ12 years) with polycythemia rubra vera (nϭ16) or hemochromatosis (nϭ4) were studied at rest and during exercise at Ϸ50% of maximal heart rate before and after venesection (500 mL; volume replaced with saline) to elicit an acute decrease in plasma viscosity at stable BP. Controls (nϭ20) underwent the same protocol with 25-mL venesection. Central BP and augmentation index were determined by tonometry. Resting LV systolic (peak longitudinal systolic strain rate and strain) and diastolic functions were determined by tissue-Doppler echocardiography. Venesection with blood volume replacement decreased viscosity (1.46Ϯ0.10 to 1.41Ϯ0.11 centipoise), protein, and hemoglobin (PϽ0.05 for all) and increased strain rate and strain (PϽ0.001 for both) in patients but not in controls (PϾ0.10 for all). There was no change in LV diastolic function (PϾ0.12 for all Key Words: blood pressure Ⅲ hemodynamics Ⅲ blood viscosity Ⅲ heart ventricles Ⅲ exercise S everal studies have demonstrated associations between blood rheological variables (eg, fibrinogen, hematocrit, blood, and plasma viscosity) and cardiovascular risk factors, including elevated blood pressure (BP), 1 raised carotid intima media thickness, 2 increased aortic pulse wave velocity, 3 incident hypertension, 4 incident cardiovascular disease, 5 and vascular and nonvascular mortality. 6 Few studies have investigated the possible mechanisms behind these associations. Recent data suggest that studying the central (ascending aortic) BP response to exercise may reveal important information relating to left ventricular (LV) function and cardiovascular risk that would otherwise be undetectable under resting conditions. 7 This could be because of the large individual variations that may exist between brachial and central systolic BPs (SBP) during exercise. 8 These changes can be seen even with light-intensity activity, similar to that of daily life. 9,10 Thus, "true" LV afterload may be significantly different between individuals with similar brachial SBP during physical activity.Using radial tonometry to estimate central BP from arterial waveforms, we found recently that men with hypercholesterolemia had significantly elevated augmentation index (AIx) and blunted pulse pressure amplification (ratio of brachial: central pulse pressure) during light exercise. 11 This was representative of increased central systolic loading (possibly affecting normal LV function) and occurred despite similar brachial SBP compared with controls. We hypothesized that this abnormal response may be related to plasma rheology, including factors such as increased viscosity, which may retard peripheral blood runoff and increase exercise AIx. The aim of this current study was to determi...