血液粘度是更早、更准确预测心血管事件风险的指标

BLOOD VISCOSITY Earlier, More Accurate Prediction of Cardiovascular Event Risk

　

Pushpa Larsen ND
2012年10月8日发表在《心肺医学》上
 
Ralph Holsworth, DO，最近和我分享了一个他多年前在科罗拉多的病人的故事。他在丹佛一家医院实习时，收治了一名被诊断为腿部血栓的病人。Holsworth博士开始给他进行低分子肝素皮下注射，同时给他注射华法林钠。他为病人治疗先天性血栓性血友病、癌症、甲状腺功能减退和其他疾病，并就这个病例咨询了血液肿瘤学家。当患者的凝血酶原时间-国际标准化比率超过2.0时，Holsworth医生按血液肿瘤学专家的医嘱安排病人出院。几分钟后，Holsworth博士的寻呼机嗡嗡作响。他的病人刚刚在停车场昏倒。他冲到急诊室，那里正在进行心肺复苏，并协助输入了代码。经过数次抢救，病人被宣布死亡。强制尸检显示病人有严重的肺栓塞，导致他的突然死亡。

　

 
直到几年之后，Holsworth博士才知道全血粘度(WBV)在血栓形成中的作用。Holsworth博士回忆说，他的病人已经出院了，并且有正常的生命体征和实验室测试结果，但是没有显示出危险的变化。Holsworth博士后来成为了临床使用血液粘度的世界领先专家之一，并问道:“我想知道，如果我能够评估他可能升高的WBV并使用抗粘剂治疗他，这个病人是否还活着。”直到那时，在将他的WBV降至安全范围后，我才把他安全出院，回到他的亲人身边。我很早就知道治疗性的国际标准化比率是不可信的。
 
什么是血液粘度（Blood viscosity)?
 
血液粘度是衡量病人血液的稠度(Thickness)和黏度(stickness)的指标。这个重要的血液动力学生物标志物决定了与血管的摩擦量，心脏必须工作的程度，以及输送到组织和器官的氧气量。它是对血液“流动能力”的直接测量，可以通过现有的自然疗法进行治疗哦。血液粘度与心血管疾病的所有已知危险因素相关，包括年龄、性别、吸烟、肥胖、炎症、胰岛素抵抗、高血压、低密度脂蛋白胆固醇（LDL)、高密度脂蛋白胆固醇(HDL)等。血粘度升高是心血管事件的独立预测因子。在爱丁堡动脉研究(Edinburgh Artery Study)中，在控制了所有其他主要危险因素后，血液粘度升高是中风风险的最强预测因子
 
了解血液粘度作为临床指标的作用是很重要的。要做到这一点，你必须了解血液流动的物理原理以及血液粘度的影响。

　

 
影响血液粘度的因素
 
决定血液粘度的五个主要因素。这些包括血细胞比容（Hematocrit)、红细胞变形性(Deformability)、血浆粘度(Viscosity)、红细胞聚集(Aggregation)和温度(Temperature)。

　

　

血细胞比容（Hemotocrit)
红细胞比容是WBV最明显的决定因素。较高比例的红细胞(rbc)导致更稠的血液。红细胞比容约占正常血粘度与高血粘度差异 的50%。

红细胞可变形性（Deformability)
红细胞的变形能力是指红细胞能以很高的速度伸长，弯曲和折叠自己，通过毛细血管的细长通道。更容易变形的红细胞导致更少的粘性血液，年轻的红细胞比老的红细胞更容易变形。红细胞变形能力是决定血液粘度的第二大因素，仅次于血细胞比容。

血浆粘度（Viscosity)
血浆粘度是指血液中液体部分的稠度(除了红细胞、白细胞和血小板)。血浆粘度受水合作用和血浆蛋白特别是高分子量蛋白如免疫球蛋白(Hemoglobin)和纤维蛋白原(Fibrinogen)的影响。

红细胞聚集(Aggregation)
红细胞聚集反应了红细胞相互吸引并结合在一起的趋势。红细胞聚集是复杂的，血浆蛋白和红细胞变形能力都起作用。

温度(Temperature)
和大多数液体一样，血液在高温下更容易流动。据估计, 1°C增加体温会导致血液粘度下降了2%。

血液粘度的物理性质
水和等离子体被认为是牛顿流体（Newtonic Fluid)。这意味着他们的粘度保持不变，无论他们流动的快或慢。另一方面，全血是一种非牛顿流体(Non-newtonic fluid)，它的粘度随速度而变化。这一点在临床监测血液粘度时变得很重要。
在舒张期，血液受到较低的压力或剪切作用。当收缩时心室收缩迅速增大，当心室放松时收缩再次减小。在这些低剪切的时期，血液变慢，血液中的细胞成分开始聚集，粘度增加。舒张期血液的粘稠度是收缩期血液的5到20倍。在接下来的心动周期中，随着剪切力的增加和血液成分的分散，粘度降低，在收缩期达到最低粘度(图1)。

　

粘性血液是研磨性血液 (Abrasive blood)
血液以层流的形式流过血管。也就是说，血液形成层流(薄层)，很容易互相滑动。从侧面观察血管，我们可以看到血液在中心层流动最快，在血管壁附近的外层流动较慢。

　

　

　

高黏度的血液不能像低黏度的血液那样平滑地滑动，导致湍流，破坏血管脆弱的内膜。在血管的曲线和分叉处也会产生湍流，尤其是靠近心脏的大血管，随着每一次心跳压力都会发生很大的变化。

　

　

血液粘度改变的临床意义
我们看到高粘度血液的后果主要是对血管的损伤，心脏的过度工作，以及对组织输送氧气的减少。高粘度的血液冲击血管壁，导致颈动脉、肺动脉和冠状动脉内膜的单细胞层磨损。身体的反应是一种保护性的适应，产生一个痂(斑块)，最终钙化以保护血管。长期的结果，当然，是增加湍流(因为不再光滑的墙壁)和不断缩小的血流通道。这一结果要求心脏更加努力工作，在更高的压力下将粘稠的血液挤出，进一步破坏内膜。在血管树的另一个极端，我们看到组织灌注减少，因为黏性血液的红细胞硬化冲刷毛细血管内壁。身体的反应是使毛细血管壁增厚，减少氧气和营养物质在组织中的扩散。这种效果在组织中最为明显，健康的毛细血管对于肾脏、眼睛、手指和脚趾等功能的正常发挥至关重要。

　

血液粘度解释斑块定位(Plague location)
血液粘度的影响，加上对封闭循环系统中血流动力学的了解，解释了为什么动脉粥样硬化斑块只在身体的特定部位被发现。如果胆固醇或炎症是主要原因，斑块将均匀分布在全身，因为胆固醇和炎症是全身性的，而不是局部性的。相反，斑块出现在大动脉的曲线和分叉处，它们位于血流调查显示乱流最严重的确切位置。我们都有这些湍流的区域，因为我们的血管树有共同的几何形状。然而，并不是每个人都会出现动脉硬化斑块。区别在于通过这些动脉的血液的粘度。胆固醇(Cholesterol)和炎症(inflammation)很重要，因为它们有助于血液粘度。

　

向组织输送氧气是由血液粘度介导的
血液向组织输送氧气的能力与血细胞比容（Hematocrit)直接相关。然而，它也与血液粘度成反比。这两个参数之间的关系用氧传递指数（oxygen delivery index)表示。在正常的男性和女性血细胞比容值范围内，改善氧传递指数与较低的血细胞比容水平相关。一个正常血细胞容量的女性实际上比一个正常血细胞容量高的男性更有能力向细胞输送氧气。高粘度血液的携氧能力下降会影响认知功能，也会影响任何组织的功能。鉴于向组织输送氧气的普遍重要性，血液粘度对健康维持和促进的相关性是显而易见的。

所有这一切都被数百项研究证明，血液粘度的升高与许多疾病有关。部分列表包括糖尿病、胰岛素抵抗、子痫前期、宫内生长迟缓、中风、短暂性缺血性发作、动脉粥样硬化、心肌梗死、外周动脉疾病、高血压、头痛、视野缺陷、青光眼、视网膜病变、霍奇金病、雷诺病、突发性耳聋、肾病综合征、阿尔茨海默病等。

性别差异（Sex difference)
众所周知，任何年龄的男性都比绝经前的女性更容易患心血管疾病。女性的风险在绝经后显著增加，年轻切除子宫的女性风险也增加了，即使她们保留了卵巢(因此有能力维持雌激素水平)。这是为什么呢? 血液粘度的主要决定因素受女性每月失血的影响很大。对红细胞压积的影响是明显的:每月减少1 - 3盎司的血液会减少红细胞的体积。对红细胞变形能力的影响可能不那么明显。由于每月出血，女性比男性产生更多的新血细胞。她的血液中含有大约80%的年轻血细胞，比男性少大约85%的老年血细胞。较老的红细胞也比较年轻的红细胞更容易聚集，影响本文所述血液粘度的第三个决定因素。此外，较老的红细胞比年轻细胞更脆弱，更容易分裂，将高分子量蛋白质血红蛋白释放到血浆中。此外，无血浆血红蛋白与一氧化氮结合，降低了一氧化氮作为血管舒张剂和血小板聚集抑制剂的功能。甚至我们的第五个行列式的血液粘度、温度、可能导致绝经前女性的降低血液粘度,因为女性的基础体温在月经周期下半段的通是增加了0.5到1°C。

高粘血症的治疗（Hyperviscosity)
我们可以使用血液粘度的5个主要决定因素来指导治疗高粘血症(hyperviscosity)。治疗的目的是优化血细胞比容(图2)，改善红细胞变形能力，降低血浆粘度，减少红细胞聚集，使体温正常。

改善血液黏度的一个简单方法是通过献血或治疗性静脉切开术（放血疗法）将血细胞比容降至最佳范围。Holsworth博士估计，42%的血细胞比容最适合男性，38%最适合女性。献血转化为实际的生活结果。在Kuopio缺血性心脏病危险因素研究中，共有24名中年男性接受了平均9年的随访。在此期间，非献血者急性心肌梗死的发生率为12.5%，几乎是献血者0.7%的18倍(P < .001)。献血是一个双赢的解决方案，但一些血库不愿进行“治疗性”静脉切除术，许多血库不会接受同一个人的献血，频率高于每2到3个月。目前正在制定每月一次的静脉切开治疗方案，可以在医生办公室根据病人的体重、血细胞比容、收缩压和舒张压的血液粘度值来进行。

　

定期献血也能改善红细胞的变形能力。在骨髓中产生的新的红细胞比旧的红细胞更具柔韧性。其他增加红细胞变形能力的方法包括通过补充营养物质(如欧米茄-3脂肪酸)来增加细胞膜的流动性，使胰岛素敏感性和血糖控制正常化。血糖失调导致渗透压波动，增加红细胞硬度。有证据表明，运动可以改善红细胞的变形能力。

　

适当的水合作用最容易改善血浆粘度，也能降低红细胞比容。发表在《航空、航天和环境医学杂志》上的研究表明，脱水（Dehydrated, Dehydration)会使收缩压血液粘稠度增加9.3%，舒张压血液粘稠度增加12.5%。对于血液粘稠度度较高的患者，建议在静脉输液前用生理盐水进行静脉补液。处理血浆蛋白也很重要，特别是当病人的低剪切(（shear rate)舒张压)粘度升高时。纳豆激酶和其他补充剂可能会降低纤维蛋白。免疫球蛋白可以通过处理食物过敏和自身免疫而减少。

　

如前所述，红细胞的变形性和血浆粘度会影响红细胞的聚集。炎症增加了影响红细胞极性的细胞因子，使它们更粘，更相互吸引。感染也增加了聚集(aggregation)的倾向。我们的自然疗法工具箱里装满了针对炎症的治疗方法，可以改善这些参数。

体温正常是一种很好的自然疗法。通过自然水疗、每天使用对比剂、优化甲状腺功能等方法来提高体温是最基本的自然疗法，可能对血液粘度有显著影响。

在动物和人类的研究中，一些草药和其他天然物质被证明可以降低血液粘度。其中包括葫芦巴和竹笋。这些草药影响血液粘度的具体决定因素尚不清楚，正如许多植物疗法一样，可能有不止一种机制在起作用。这些天然的治疗方法有很多，它们本身就值得一篇完整的文章。

抗血液粘疗法
Holsworth博士描述的病人接受了肝素和华法林的治疗，但仍然出现了导致他死亡的血凝块。我们倾向于认为华法林是一种血液稀释剂，但根据Holsworth博士的说法，他经常看到接受华法林治疗的患者血液粘度升高。Holsworth博士将华法林比作混凝土中的添加剂，它们会减慢混凝土凝固所需的时间。它们实际上不会改变水泥的粘度。阿司匹林也不会降低血液粘度。
另一方面，他汀类药物会降低血液粘度，这可能是其有效性的原因之一。当然，他汀类药物也有自己的问题。当患者脱离他汀类药物时，最好谨慎监测血液粘度。

测量全血粘度（WBV）
到目前为止，血液粘度在临床实践中一直是一个被忽视的参数，尽管有大量的研究关于它的重要性和相关性广泛的条件。大多数粘度测试都是针对血浆粘度进行的，这在特定条件的狭窄范围内是有用的。你们会记得，等离子体是牛顿流体，它的粘度与剪切力无关。

WBV的测量很少由初级护理医师进行，只能通过参考实验室进行。全血粘度通常是用粘度计测量的，粘度计是一种较老的技术，最初是用来测量室内涂料或机油的粘度。它产生的单一测量值大致相当于收缩压下血液的粘度，此时血液的流动性最强，黏度最低。然而，正如我们所见，血液粘度是动态的。在收缩压剪切速率(高剪切速率high shear rate)下显示正常粘度的血液，在舒张压剪切速率(低剪切速率)下可能会有不同的结果。

最新和最先进的测试使用的是一种自动扫描毛细管粘度计，它能够通过一次连续测量测量心脏周期(10000剪切速率)的完整生理值范围内的粘度。随后将其简化为两种测量方法，即高剪切(收缩压)粘度和低剪切(舒张压)粘度。这个术语不是指病人的收缩压和舒张压，而是指在收缩压和舒张压期间的剪切速率。这些剪切速率在血液粘度研究文献中已经得到了证实。

哪些人应该定期检测血粘度?
Holsworth博士认为，血液粘度是另一个重要的信号，应该像监测血压一样定期监测。当然，当我们观察与血液粘度升高相关的条件的数量时，我们会发现很少有病人对血液粘度进行监测是不合理的。检测血液粘度最明显的患者是那些具有明确心血管危险因素的患者，包括吸烟者、肥胖者、有血栓病史的患者、胰岛素抵抗者、高血压患者、或其他升高的标志物，如C反应蛋白、糖化血红蛋白、低密度脂蛋白胆固醇(LDL)、纤维蛋白原、同型半胱氨酸等。在这个列表中还包括服用降低月经频率的口服避孕药的妇女。这些避孕措施真是祸不单行。它们不仅削弱了每月失血的自然优势，而且口服雌激素会增加血栓形成的风险。在这个列表中，我还会加上任何患有肾病、青光眼、黄斑变性、认知功能改变或自身免疫性疾病的人。我最后的两个个人选择是，第一，孕妇或有子痫前期或宫内发育迟缓病史的女性，第二，年轻的男性运动员。

为什么是年轻的男运动员? 最近，我咨询了一名23岁男子的血液粘度分布图。他的血液粘度值，包括收缩压和舒张压都很高。这个年轻人是长跑运动员，他对自己的身体照顾得很好，通常保持良好的水分，实验室检测值和血压正常。我对此很好奇，因为人们不时会听到年轻运动员在比赛中途或赛后倒地身亡的消息。在我看来，这是一个惊人的数据:在美国，每3天就有一名年轻的运动员死于心脏骤停。

孕妇通常被认为有较低的血液粘度问题的风险，因为在怀孕期间，血容量的增加通常与血液稀释和轻度的血细胞压降有关。然而，妊娠并发症(如子痫前期和宫内生长迟缓)与血液粘度升高有关。Holsworth博士的观察表明，在高血压和其他子痫前期症状出现前6周，血液粘度开始上升。这是一个巨大的临床干预窗口。

为什么需要检查血粘度?
一位内科医生最近对我说:“我已经知道我的病人可能会因为他们的风险因素而血液粘度很高。为什么不治疗他们呢?为什么要费心去测试呢?“我测试是因为我想知道我正在处理的问题有多严重。我测试我的治疗是否有效，或者我们是否需要更积极地治疗。

血液粘度比其他任何风险因素都能更早、更准确地预测心血管事件风险。通过对331名中年高血压患者的研究，明确了血液粘度的预测价值。这些人按血液粘度分为3组，随访5年。在研究期间，高粘度组的男性心血管事件最多。低粘度组的人——记住他们也有高血压——有最长的无事件生存期。本文开头提到的爱丁堡动脉研究发现，血液粘度对中风的预测价值最高。

改善患者的血液粘度对于降低心脑血管事件的风险，以及改善任何与组织灌注密切相关的病症都有很大的希望。心脏病专家在监测高危病人的血液粘度方面做得好吗? 当然,他们会。然而，大多数病人只有在心脏病发作或出现症状后才去看心脏病专家。对于自然疗法医生和其他对预防疾病和帮助病人茁壮成长感兴趣的初级保健提供者来说，血液粘度是一种非常宝贵的工具，它可以使疾病的早期发现成为可能。这样可以更快的治疗，更少的伤害和更好的结果。这样，我们就更接近于实现我们对待事业的信条。

Pushpa Larsen, ND毕业于Bastyr大学(Kenmore，华盛顿)，接受自然疗法医学、自然疗法助产学、灵性、健康和医学方面的培训。她曾在Bastyr大学研究所担任研究临床医师，并在Bastyr大学担任附属临床教员，在她的诊所训练学生。她在华盛顿州西雅图实习了10年，直到3年前加入华盛顿州莱顿市的Meridian Valley 实验室（Meridian Valley Lab)，成为一名咨询医师。她每年都要向数百名医生咨询如何使用和解释Meridian Valley 实验室提供的检测方法。

　

　

　

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BLOOD VISCOSITY Earlier, More Accurate Prediction of Cardiovascular Event Risk

Pushpa Larsen, ND

By Editor   Posted October 8, 2012   In Cardiopulmonary Medicine 

 

Ralph Holsworth, DO, recently shared a story with me about a patient he had in Colorado many years ago. He was an intern in a Denver hospital when he admitted a patient diagnosed as having a blood clot in his leg. Dr Holsworth started him on low-molecular-weight heparin subcutaneous injections concurrently with warfarin sodium. He worked the patient up for congenital thrombophilias, cancer, hypothyroidism, and other conditions, and consulted with hematology-oncology on the case. When the patient’s prothrombin time–international normalized ratio exceeded 2.0, Dr Holsworth was instructed by hematology-oncology to discharge the patient. A few minutes later, Dr Holsworth’s pager buzzed. His patient had just collapsed in the parking lot. He rushed down to the emergency department, where cardiopulmonary resuscitation was in progress and assisted in the code. The patient was pronounced dead after several attempts at resuscitation. A mandatory autopsy revealed that the patient had a major pulmonary embolism, resulting in his sudden death.

 

It was not until several years later that Dr Holsworth learned of the role of whole blood viscosity (WBV) in the formation of thrombi. Dr Holsworth recalled that his aforementioned patient had been discharged with normal vital signs and laboratory test results that provided no indication of the evolving danger. Dr Holsworth later became one of the world’s leading experts in the use of blood viscosity in a clinical setting and asked: “I wonder if this patient would be alive had I been able to evaluate his likely elevated WBV and treat him with antiviscogenic agents. Only then, after lowering his WBV to a safe range, would I have discharged this patient safely to home to his loved ones. I learned early on that a therapeutic international normalized ratio was not to be trusted.”

 

What Is Blood Viscosity?

 

Blood viscosity is a measurement of the thickness and stickiness of a patient’s blood. This important hemodynamic biomarker determines the amount of friction against the blood vessels, the degree to which the heart must work, and the quantity of oxygen delivery to the tissues and organs. It is a direct measure of the “flow ability” of blood and is modifiable with existing naturopathic therapies. Blood viscosity is correlated with all known risk factors for cardiovascular disease, including age, sex, smoking, obesity, inflammation, insulin resistance, high blood pressure, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, and others.1-5 Elevated blood viscosity is a strong independent predictor of cardiovascular events.6 In the Edinburgh Artery Study, elevated blood viscosity was the strongest predictor of stroke risk, after controlling all other major risk factors.7,8

 

It is important to understand the role of blood viscosity as a clinical marker. To do so, one must know something about how the physics of blood flow works and about what affects blood viscosity.

 

Factors Affecting Blood Viscosity

 

Five primary factors determine blood viscosity. These include hematocrit, erythrocyte deformability, plasma viscosity, erythrocyte aggregation, and temperature.1

 

Hematocrit

 

Hematocrit is the most obvious determinant of WBV. A higher percentage of red blood cells (RBCs) results in thicker blood. Hematocrit accounts for about 50% of the difference between normal blood viscosity and high blood viscosity.

 

Erythrocyte Deformability

 

Erythrocyte deformability refers to the ability of RBCs to elongate at high velocity and to bend and fold themselves to pass through the slender passageways of the capillaries. More flexible RBCs result in less viscous blood, and young RBCs are more flexible than older RBCs. Erythrocyte deformability is the second most important determinant of blood viscosity, after hematocrit.

 

 

 

 

Plasma Viscosity

 

Plasma viscosity refers to the thickness of the fluid portion of blood (everything except for RBCs, white blood cells, and platelets). Plasma viscosity is highly affected by hydration and by plasma proteins, especially high-molecular-weight proteins such as immunoglobulins and fibrinogen.

 

Erythrocyte Aggregation

 

Erythrocyte aggregation reflects the tendency of RBCs to be attracted to each other and to stick together. Red blood cell aggregation is complex, with both plasma proteins and RBC deformability having a role.

 

Temperature

 

As with most fluids, blood flows more easily at higher temperatures. It is estimated that a 1°C increase in body temperature results in a 2% decrease in blood viscosity.9

 

The Physics of Blood Viscosity

 

Water and plasma are considered newtonian fluids. This means that their viscosity remains the same whether they are flowing fast or slowly. Whole blood, on the other hand, is a non-newtonian fluid, and its viscosity changes with its velocity. This point becomes important clinically when monitoring blood viscosity.

 

During diastole, blood is subject to lower pressures, or shear. Shear increases rapidly as the ventricles contract in systole and then decreases again as the ventricles relax. During these periods of low shear, the blood slows, cellular components of blood begin to aggregate, and viscosity increases. Blood at diastole can be anywhere from 5 to 20 times as viscous as the same blood at systole. In the next cardiac cycle, viscosity decreases as shear increases and blood components are dispersed, reaching its lowest viscosity at the height of systole (Figure 1).

 

Viscous Blood Is Abrasive Blood

 

Blood flows through the vessels in what is described as laminar flow. That is, the blood forms layers (lamina) that slide easily over each other. Looking at the blood vessel from the side, we would see the fastest flowing blood in the center layers, with slower moving blood in the outer layers near the wall of the vessel. Highly viscous blood does not slide as smoothly as less viscous blood, leading to turbulence that can damage the delicate intima of the blood vessel. Turbulence is also generated at curves and bifurcations in blood vessels, particularly the large vessels nearest the heart, which are subject to great changes in pressure with each heartbeat.

 

Clinical Implications of Altered Blood Viscosity

 

We see the consequences of hyperviscous blood primarily in damage to the blood vessels, in overwork of the heart, and in decreased delivery of oxygen to the tissues. Highly viscous blood pounding against the walls of the blood vessels leads to abrasion of the single-cell layer of the intima in the carotid, pulmonary, and coronary arteries. The body responds with a protective adaptation, creating a scab (plaque), which eventually calcifies in an effort to protect the blood vessel. The longer-term result, of course, is increased turbulence (because of the no-longer smooth wall) and an ever-narrowing channel for blood flow. This result requires the heart to work harder, pushing the viscous blood out at even higher pressures, further damaging the intimal layer. At the other extreme of the vascular tree, we see decreased perfusion of the tissues as the stiffened erythrocytes of viscous blood scour the capillary linings. The body responds by thickening the capillary walls, decreasing diffusion of oxygen and nutrients into the tissues. This effect is most pronounced in tissues where healthy capillaries are essential for unimpaired function such as the kidneys, eyes, fingers, and toes.

 

Blood Viscosity Explains Plaque Localization

 

The effects of blood viscosity, taken together with an understanding of the dynamics of blood flow in a closed circulatory system, explain why it is that atherosclerotic plaques are found only in specific locations in the body.1,10 If cholesterol or inflammation was the primary culprit, plaques would be evenly distributed throughout the body because cholesterol and inflammation are generalized rather than localized. Instead, plaques are found in the curves and bifurcations of the large arteries, and they are located in the exact places where blood flow investigations show that turbulence is the greatest. We all have these areas of turbulent blood flow because we share a common geometry of our vascular tree. Yet, not everyone develops artherosclerotic plaques. The difference lies in the viscosity of the blood traveling through those arteries. Cholesterol and inflammation are important because they contribute to blood viscosity.

 

Delivery of Oxygen to the Tissues Is Mediated by Blood Viscosity

 

The capacity of blood to carry oxygen to the tissues is directly correlated with hematocrit. However, it is also inversely correlated with blood viscosity. The relationship of these 2 parameters is expressed as the oxygen delivery index. Within the limits of normal hematocrit values for men and women, improved oxygen delivery index is associated with lower hematocrit levels. A woman with a normal hematocrit actually has a greater ability to deliver oxygen to cells than a man with a higher, but normal, hematocrit.11 The decreased oxygen-carrying capacity of higher-viscosity blood affects cognitive function, as well as the function of any tissue to which robust oxygen delivery is essential (such as the placenta). Given the universal importance of oxygen delivery to the tissues, the relevance of blood viscosity to health maintenance and promotion is clear.

 

All of this is borne out by hundreds of studies showing that elevated blood viscosity is associated with a host of conditions. A partial list includes diabetes mellitus, insulin resistance, preeclampsia, intrauterine growth retardation, stroke, transient ischemic attacks, atherosclerosis, myocardial infarction, peripheral artery disease, hypertension, headaches, visual field defects, glaucoma, retinopathy, Hodgkin disease, Raynaud disease, sudden deafness, nephrotic syndrome, Alzheimer disease, and more.12-22

 

The Sex Difference

 

It is well known that men of any age are at higher risk for cardiovascular events than premenopausal women.11,23 A woman’s risk increases significantly after menopause, and younger women who have hysterectomies are also at increased risk, even if they retain their ovaries (thus an ability to maintain estrogen levels). Why is this? The primary determinants of blood viscosity are highly affected by a woman’s monthly blood loss. The effect on hematocrit is obvious: the monthly loss of 1 to 3 oz of blood will decrease the volume of RBCs. The effect on RBC deformability may be less obvious. Because of monthly bleeding, a woman makes more new blood cells than a man. Her blood contains about 80% more young blood cells and about 85% fewer old blood cells.11 Older RBCs are also more likely to aggregate than are younger RBCs, affecting the third determinant of blood viscosity described herein. In addition, older RBCs are more fragile than younger cells and are more likely to break apart, releasing hemoglobin, a high-molecular-weight protein, into the plasma. Furthermore, plasma-free hemoglobin binds nitric oxide, reducing the ability of nitric oxide to perform its functions as a vasodilator and as an inhibitor of platelet aggregation. Even our fifth determinant of blood viscosity, temperature, may contribute to the lower blood viscosity of premenopausal women because a woman’s basal body temperature is normally increased by 0.5 to 1°C for the second half of her menstrual cycle.

 

Treatments for Hyperviscosity

 

We can use the 5 primary determinants of blood viscosity to guide our treatments for hyperviscosity. The objectives of therapy are to optimize hematocrit (Figure 2), improve RBC deformability, decrease plasma viscosity, reduce RBC aggregation, and normalize body temperature.

 

An easy way to improve blood viscosity is to decrease hematocrit to optimal ranges through blood donation or therapeutic phlebotomy. Dr Holsworth estimates that a hematocrit of 42% is optimal for men, while 38% is optimal for women. Blood donation translates into real-life results. In the Kuopio Ischemic Heart Disease Risk Factor Study,24 a total of 2862 middle-aged men were followed up for a mean of 9 years. During that time, the rate of acute myocardial infarction among non-blood donors was 12.5%, almost 18 times the 0.7% rate among blood donors (P < .001). Blood donation is a win-win solution, but some blood banks shy away from performing “therapeutic” phlebotomy, and many blood banks will not accept donation from the same individual more often than every 2 to 3 months. Protocols are being developed for monthly therapeutic phlebotomy that can be performed in the physician’s office based on a patient’s weight, hematocrit, and systolic and diastolic blood viscosity values.

 

Erythrocyte deformability is also improved by regular blood donation. New RBCs being produced in bone marrow will be more flexible than older RBCs. Other approaches to increasing RBC deformability include increasing membrane fluidity with nutrient supplementation (such as omega-3 fatty acids) and normalizing insulin sensitivity and blood glucose control. Blood glucose dysregulation results in fluctuations in osmolality that increase RBC rigidity. Evidence also shows that exercise can improve RBC deformability.25

 

Plasma viscosity is most easily improved with adequate hydration, which can also decrease hematocrit. Research published in the Aviation, Space, and Environmental Medicine journal demonstrated that dehydration increases systolic blood viscosity by 9.3% and diastolic blood viscosity by 12.5%.26 For patients with high blood viscosity, intravenous hydration with normal saline before phlebotomy is advised. It is also important to address plasma proteins, particularly if a patient’s low shear (diastolic) viscosity is elevated. Nattokinase and perhaps other supplements can reduce fibrin. Immunoglobulins can be decreased by addressing food allergies and autoimmunity.

 

Red blood cell aggregation is affected by RBC deformability and by plasma viscosity, as already noted. Inflammation increases cytokines that affect the polarity of RBCs, making them stickier and more attracted to each other. Infection also increases the tendency to aggregation. Our naturopathic toolboxes are filled with therapies that target inflammation and can improve these parameters.

 

Normalizing body temperature is just good naturopathic medicine. Increasing the body temperature with constitutional hydrotherapy, the use of daily contrast showers, and optimization of thyroid function are fundamental naturopathic therapies that may have significant effects on blood viscosity.

 

Several herbs and other natural substances have been shown to lower blood viscosity in animal and human studies.27-30 These include Trigonella foenum and bamboo shoot. The specific determinants of blood viscosity that these herbs affect are unclear, and as with many botanical treatments, more than 1 mechanism may be at play. There are many of these natural therapeutic possibilities, and they are worthy of an entire article by themselves.

 

Allopathic Antiviscogenic Therapies

 

Dr Holsworth’s patient described herein was treated with heparin and warfarin yet still developed a blood clot that killed him. We tend to think of warfarin as a blood thinner, but according to Dr Holsworth, he frequently sees patients receiving warfarin therapy who have elevated blood viscosity. Dr Holsworth likens warfarin to additives in concrete that slow down the time it takes for the concrete to set. They do not actually change the viscosity of the cement. Aspirin also does not decrease blood viscosity.

 

Statins, on the other hand, decrease blood viscosity, and that may be a reason for their effectiveness. Statins come with their own problems, of course. When weaning patients off statins, it would be prudent to monitor blood viscosity.

 

Measuring WBV

 

Until now, blood viscosity has been an overlooked parameter in clinical practice, despite the wealth of research on its importance and relevance to a wide range of conditions. Most viscosity testing has been for plasma viscosity, which has usefulness for a narrow range of specific conditions. Plasma, you will recall, is a newtonian fluid, and its viscosity is independent of shear.

 

The measurement of WBV, rarely ordered by primary care physicians, has been available only through reference laboratories. Whole blood viscosity is generally measured using a viscometer, an older technology originally developed to measure the viscosity of house paint or motor oil. It yields a single measurement that is roughly equivalent to the viscosity of the blood at systolic pressures, when blood is the most fluid and the least sticky. However, as we have seen, blood viscosity is dynamic. Blood that exhibits normal viscosity at systolic shear rates (high shear) may tell a very different story at diastolic shear rates (low shear).

 

The newest and most advanced testing uses an automated scanning capillary tube viscometer, which is capable of measuring viscosity over the complete range of physiological values experienced in a cardiac cycle (10 000 shear rates) with a single continuous measurement. It is subsequently simplified into 2 measurements, namely, a high shear (systolic) viscosity and a low shear (diastolic) viscosity. This terminology does not refer to the patient’s systolic and diastolic blood pressures but to shear rates that are typically found during systole and diastole. Those shear rates are well established in the blood viscosity research literature.

 

Who Should Be Tested?

 

Dr Holsworth believes that blood viscosity is another vital sign that should be monitored regularly just as one would monitor blood pressure. Certainly, when one looks at the number of conditions associated with elevated blood viscosity, it becomes clear that there are few patients for whom monitoring blood viscosity would be unreasonable. The most obvious patients to test for blood viscosity are those with clear cardiovascular risk factors, including smokers, obese individuals, patients with a history of blood clots, and those with insulin resistance, hypertension, or other elevated markers such as C-reactive protein, glycated hemoglobin, low-density lipoprotein cholesterol, fibrinogen, homocysteine, and others. Also included in this list would be women taking oral contraceptives that decrease the frequency of menses. These contraceptives are a double whammy. Not only do they attenuate the natural advantage of monthly blood loss, but the use of oral estrogens is associated with an increased risk for developing blood clots. To this list, I would add anyone with kidney disease, glaucoma, macular degeneration, changes in cognitive function, or autoimmune diseases. My final 2 personal picks are, first, pregnant women or women with any history of preeclampsia or intrauterine growth retardation and, second, young male athletes.

 

Why young male athletes? Recently, I consulted with a physician on a blood viscosity profile for a 23-year-old man. His blood viscosity values, both systolic and diastolic, were critically high. This young man was a long-distance runner, who took superb care of his body, generally stayed well hydrated, and had otherwise normal laboratory test values and blood pressure. I became curious about this because one hears periodically of young athletes dropping dead in the middle of a game or after a race. A little digging uncovered what to me was a surprising statistic: a young athlete dies of sudden cardiac arrest every 3 days in the United States.31 Ninety percent of those athletes are male.

 

Pregnant women would normally be considered at lower risk for blood viscosity issues because in pregnancy the increased blood volume is usually associated with hemodilution and with a mildly decreased hematocrit. However, complications of pregnancy (such as preeclampsia and intrauterine growth retardation) are associated with elevated blood viscosity. Dr Holsworth’s observation has been that blood viscosity starts to increase about 6 weeks before the development of hypertension and other signs of preeclampsia. That is a huge clinical window for intervention.

 

Why Not Just Treat?

 

A physician recently said to me, “I already know that my patient is likely to have high blood viscosity because of their risk factors. Why not just treat them? Why bother to test?” I test because I want to know how severe a problem I am dealing with. I test to know whether or not my treatments are working adequately or if we need to treat more aggressively.

 

Blood viscosity allows for earlier, more accurate prediction of cardiovascular event risk than any other risk factor. The predictive value of blood viscosity is made clear in looking at a study7 of 331 middle-aged men with hypertension. These men were stratified into 3 groups by blood viscosity and were followed up for a mean of 5 years. The men in the highest viscosity group had the most cardiovascular events during the study period. The men in the lowest viscosity group—remember that they also had high blood pressure—had the longest event-free survival. The Edinburgh Artery Study,8 as mentioned at the beginning of this article, found that blood viscosity had the highest predictive value for stroke.

 

Improving our patients’ blood viscosity holds great promise for reducing the risk for cardiovascular and cerebrovascular events, as well as improving health in any condition where perfusion is important. Would cardiologists do well to monitor their high-risk patients’ blood viscosity? Surely, they would. However, most patients see a cardiologist only after they have already had a heart attack or are experiencing symptoms. For naturopathic physicians and other primary care providers interested in preventing disease and helping our patients to thrive, blood viscosity is an invaluable tool that permits earlier detection of developing disease. This allows for sooner treatment, less damage, and improved outcomes. In this way, we come closer to fulfilling our precept to treat the cause.

 

Pushpa Larsen, ND graduated from Bastyr University (Kenmore, Washington), with training in naturopathic medicine, naturopathic midwifery, and spirituality, health and medicine. She has worked as a research clinician for the Bastyr University Research Institute and as an affiliate clinical faculty member at Bastyr University, training students in her clinic. She practiced in Seattle, Washington, for 10 years before joining Meridian Valley Lab, Renton, Washington, as a consulting physician almost 3 years ago. She consults with hundreds of physicians every year on the use and interpretation of tests offered by Meridian Valley Lab.

 

https://ndnr.com/cardiopulmonary-medicine/blood-viscosity/