Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors

Most non-communicable diseases involve inflammatory changes in one or more vascular systems, and there is considerable evidence that unliganded iron plays major roles in this Most studies concentrate on biochemical changes, but there are important biophysical correlates Here we summarize recent microscopy-based observations to the effect that iron can have major effects on erythrocyte morphology, on erythrocyte deformability and on both fibrinogen polymerization and the consequent structure of the fibrin clots formed, each of which contributes significantly and negatively to such diseases We highlight in particular type 2 diabetes mellitus, ischemic thrombotic stroke, systemic lupus erythematosus, hereditary hemochromatosis and Alzheimer's disease, while recognizing that many other diseases have co-morbidities (and similar causes) Inflammatory biomarkers such as ferritin and fibrinogen are themselves inflammatory, creating a positive feedback that exacerbates disease progression The biophysical correlates we describe may provide novel, inexpensive and useful biomarkers of the therapeutic benefits of successful treatments

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Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases

Blood viscosity values and biochemical correlates in healthy adults

Markers of atherosclerotic development in children with familial hypercholesterolemia: a literature review.

Introduction Testosterone replacement therapy (TRT) is a common treatment for hypogonadism in aging males. Men with low to low‐normal levels of testosterone have documented benefit from hormone replacement. Recent meta‐analyses have revealed that increases in hemoglobin (Hb) and hematocrit (Hct) are the variants most commonly encountered. Clinically, this response is described as erythrocytosis or polycythemia secondary to TRT. However, the recent Food and Drug Administration warning regarding the risk for venothromboembolism (VTE) has made the increases in Hb and Hct of more pertinent concern. The risks associated with androgen replacement need further examination. Aim To review the available literature on erythrocytosis and polycythemia secondary to TRT. To discuss potential etiologies for this response, the role it plays in risk for VTE, and recommendations for considering treatment in at‐risk populations. Methods A literature review was performed through PubMed regarding TRT and erythrocytosis and polycythemia. Main Outcome Measures To assess the mechanisms of TRT‐induced erythrocytosis and polycythemia with regard to basic science, pharmacologic preparation, and route of delivery. To review Hct and risk for thrombotic events. To offer clinical suggestions for therapy in patients at risk for veno‐thrombotic events. Results Men undergoing TRT have a 315% greater risk for developing erythrocytosis (defined as Hct > 0.52) when compared with control. Mechanisms involving iron bioavailability, erythropoietin production, and bone marrow stimulation have been postulated to explain the erythrogenic effect of TRT. The association between TRT‐induced erythrocytosis and subsequent risk for VTE remains inconclusive. Conclusions All TRT formulations cause increases in Hb and Hct, but injectables tend to produce the greatest effect. The evidence regarding the risk for VTE with increased Hct is inconclusive. For patients with risk factors for veno‐thrombotic events, formulations that provide the smallest effect on blood parameters hypothetically provide the safest option. Further trials are needed to fully evaluate the hematological side effects associated with TRT. Jones SD Jr, Dukovac T, Sangkum P, Yafi FA, and Hellstrom WJG. Erythrocytosis and polycythemia secondary to testosterone replacement therapy in the aging male. Sex Med Rev 2015;3:101–112.

Erythrocytosis and Polycythemia Secondary to Testosterone Replacement Therapy in the Aging Male

The pathogenesis of several major cardiovascular diseases, including atherosclerosis, hypertension, and the metabolic syndrome, is not widely understood because the role of blood viscosity is overlooked. Low-density lipoprotein accelerates atherosclerosis by increasing blood viscosity in areas of low flow or shear, predisposing to thrombosis. Atherosclerotic plaques are organized mural thrombi, as proposed by Duguid in the mid-twentieth century. High-density lipoprotein protects against atherosclerosis by decreasing blood viscosity in those areas. Blood viscosity, at the least, contributes to hypertension by increasing systemic vascular resistance. Because flow is inversely proportional to viscosity, hyperviscosity decreases perfusion and glucose utilization by skeletal muscle, contributing to hyperglycemia in the metabolic syndrome. Therapeutic phlebotomy reduces blood pressure and serum glucose levels in the metabolic syndrome by improving blood viscosity.

https://journals.sagepub.com/doi/pdf/10.1177/1753944714553226

The role of chronic hyperviscosity in vascular disease

Renewed interest in the age-old concept of "bloodletting", a therapeutic approach practiced until as recently as the 19th century, has been stimulated by the knowledge that blood loss, such as following regular donation, is associated with significant reductions in key hemorheological variables, including whole blood viscosity (WBV), plasma viscosity, hematocrit and fibrinogen. An elevated WBV appears to be both a strong predictor of cardiovascular disease and an important factor in the development of atherosclerosis. Elevated WBV through wall shear stress is the most direct physiological parameter that influences the rupture and erosion of vulnerable plaques. In addition to WBV reduction, phlebotomy may reduce an individual's cardiovascular risk through reductions in excessive iron, oxidative stress and inflammation. Reflecting these findings, blood donation in males has shown significant drops in the incidence of cardiovascular events, as well as in procedures such as percutaneous transluminal coronary angioplasty and coronary artery bypass grafting. Collectively, the available data on the benefits of therapeutic phlebotomy point to the importance of monitoring WBV as part of a cardiovascular risk factor, along with other risk-modifying measures, whenever an increased cardiovascular risk is detected. The development of a scanning capillary tube viscometer allows the measurement of WBV in a clinical setting, which can prove to be valuable in providing an early warning sign of an increased risk of cardiovascular disease.

Cardiovascular benefits of phlebotomy: relationship to changes in hemorheological variables

Previous research has shown fluid replacement beverages ingested after exercise can affect hydration biomarkers. No specific hydration marker is universally accepted as an ideal rehydration parameter following strenuous exercise. Currently, changes in body mass are used as a parameter during post-exercise hydration. Additional parameters are needed to fully appreciate and better understand rehydration following strenuous exercise. This randomized, double-blind, parallel-arm trial assessed the effect of high-pH water on four biomarkers after exercise-induced dehydration. One hundred healthy adults (50 M/50 F, 31 ± 6 years of age) were enrolled at a single clinical research center in Camden, NJ and completed this study with no adverse events. All individuals exercised in a warm environment (30 °C, 70% relative humidity) until their weight was reduced by a normally accepted level of 2.0 ± 0.2% due to perspiration, reflecting the effects of exercise in producing mild dehydration. Participants were randomized to rehydrate with an electrolyzed, high-pH (alkaline) water or standard water of equal volume (2% body weight) and assessed for an additional 2-h recovery period following exercise in order to assess any potential variations in measured parameters. The following biomarkers were assessed at baseline and during their recovery period: blood viscosity at high and low shear rates, plasma osmolality, bioimpedance, and body mass, as well as monitoring vital signs. Furthermore, a mixed model analysis was performed for additional validation. After exercise-induced dehydration, consumption of the electrolyzed, high-pH water reduced high-shear viscosity by an average of 6.30% compared to 3.36% with standard purified water (p = 0.03). Other measured biomarkers (plasma osmolality, bioimpedance, and body mass change) revealed no significant difference between the two types of water for rehydration. However, a mixed model analysis validated the effect of high-pH water on high-shear viscosity when compared to standard purified water (p = 0.0213) after controlling for covariates such as age and baseline values. A significant difference in whole blood viscosity was detected in this study when assessing a high-pH, electrolyte water versus an acceptable standard purified water during the recovery phase following strenuous exercise-induced dehydration.

https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1007&context=student_papers

Effect of electrolyzed high-pH alkaline water on blood viscosity in healthy adults

ContextCardiovascular disease (CVD) is the leading cause of on-duty death among firefighters, totaling 45% of on-duty fatalities. Heat stress and fluid losses can result in decreases in cardiac output of firefighters, despite sus- tained tachycardia and maximally elevated heart rate dur- ing emergencies. Measurements of whole blood viscosity (WBV) may serve as an independent biomarker of the hydration and dehydration states of on-duty firefighters. ObjectiveThe current pilot study investigates the effects of a strenuous firefighting simulation and subsequent rehydration on WBV and other biological metrics in nine healthy, nonsmoking firefighters to (1) determine whether dehydration and rehydration result in detectable changes in WBV and (2) compare WBV with the results from a range of conventional medical tests. DesignThe research team designed a single-center, unblinded pilot study. SettingFire Training Division, 1900 Lind Ave SW, Renton, WA, 98057. ParticipantsParticipants were 9 healthy, nonsmoking firefighters who were volunteers. Outcome Measure(s) • Vital signs, traditional medical blood tests, and WBV were measured for each firefighter (1) at baseline, (2) after exercise but before rehydration with alkaline water, and (3) postexercise and after rehy- dration. Hematocrit (HCT), hemoglobin (Hb), and WBV increased after exercise and before rehydration. ResultsDehydration during the mock fire drill resulted in elevated WBV at both low- and high-shear rates. HCT and Hb increased due to dehydration and hemoconcen- tration. Hb and HCT returned to baseline values after exercise and rehydration, and while WBV improved, base- line values were not restored. After exercise but before rehydration, WBV changes were significantly larger than HCT and Hb changes, suggesting the profound influence of hydration states on WBV. ConclusionsWBV measurements were better determi- nants of hydration states than HCT or Hb and should be performed to monitor the cardiovascular health of at-risk firefighters. (Altern Ther Health Med. 2013;19(4):44-49.)

Effect of hydration on whole blood viscosity in firefighters.

Sir,Approximately 500,000 cardiopulmonary bypass (CPB) procedures using extracorporeal circulation are per-formed annually in the United States of America.. For decades, attention has focused on cerebral complications as a source of morbidity and disability post procedures. These deficits include impaired consciousness, seizures, cognitive impairment (memory, attention deficits, lan-guage difficulty) and stroke, all potentially limiting the ability to function independently. The reported inci-dence of neurological complications varies widely from 7 to 61% for transient deficits and 1.6 to 23% for perma-nent deficits.

Ralph E. Holsworth

Papers

The role of chronic hyperviscosity in vascular disease

Cardiovascular benefits of phlebotomy: relationship to changes in hemorheological variables

Effect of electrolyzed high-pH alkaline water on blood viscosity in healthy adults

Effect of hydration on whole blood viscosity in firefighters.

Importance of monitoring blood viscosity during cardiopulmonary bypass