功能医学指导下的高血压干预案例分析（下）

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DISCUSSION

Hypertension is directly or indirectly associated with five of the top nine causes of death in the U.S., including heart disease, cerebrovascular disease, diabetes, renal disease, and essential hypertension.' Lifestyle risk factors play a significant role in hypertension etiology, including poor diet and nutrition, unbalanced salt and potassium intake, inactivity, and

smoking. There is also a recognized genetic component.' Essential element deficiency, in particular that of magnesium, is strongly implicated as a contributing factor (Table 1).

讨论

在美国，高血压与排在前九位的死亡原因中的五个有着直接或间接地联系，包括心脏病、脑血管疾病、糖尿病、肾病和原发性高血压。生活方式中存在的风险在高血压致病因素中也占有关键的地位，包括饮食和营养不良、盐和钠摄入失衡、缺乏体育锻炼以及吸烟等，此外，遗传因素也值得我们注意，同时，必要元素的缺乏尤其是镁，也是引发高血压的一个重要原因。

The patient had multiple imbalances that can contribute to hypertension, including an elevated ADMA (Figure 1). ADMA has been shown to impair nitric oxide function, and therefore has adverse effects on blood pressure, erectile function, and other nitric oxide-dependent activities. Treatment with arginine and N-acetylcysteine has been shown to reduce both systolic and diastolic mean arterial blood pressure, total cholesterol, oxidized LDL, and high-sensitivity C-reactive protein. ADMA synthesis, clearance, and regulation of nitric oxide synthase are illustrated in Figure 9. Arginine, the substrate for nitric oxide, was high-normal in JF. Any elevation of ADMA may cause a relative L-arginine deficiency resulting in lowered nitric oxide production. Thus, supplementation with arginine, even in states of apparent sufficiency, may be indicated.In this case, treatment included sustained-release arginine to address both the high blood pressure and erectile dysfunction.

患者有多种会导致高血压的失衡现象，其中就包括ADMA水平上升。ADMA已经被证实会影响一氧化氮的功能，所以对于血压、勃起功能和其他一氧化氮依赖性活动有负面影响。精氨酸和N-乙酰半胱氨酸疗法被证实可以降低舒张动脉压和收缩动脉压，总胆固醇、氧化型低密度脂蛋白和超敏C反应蛋白。ADMA的生成、消除和一氧化氮合酶的调节如图9所示。作为一氧化氮合成的底物，精氨酸在JF的体内处于高正常水平。任何ADMA水平的上升都有可能引起相关的L精氨酸缺乏，这会降低一氧化氮的生成。所以，即使在患者精氨酸很充足的情况下，也可能需要补充。在这个案例中，缓释精氨酸被应用于治疗高血压和勃起障碍。

图9：ADMA的合成、清除&NOS调节

Laboratory assessment also revealed elevated quinolinate and hs-CRP (Figure 2), both of which are associated with systemic inflammation, possibly from insulin resistance and/or an occult infection (e.g., periodontal disease). Anti-inflammatory treatment approaches were used, including ascorbic acid and magnesium supplementation. JF was also put on an oral hygiene regimen using an oral irrigation system, and was instructed to avoid sugars and processed carbohydrates. Cinnamon was prescribed because of its apparent favorable effect on insulin sensitivity and its antimicrobial properties.

根据实验室分析，可能由于胰岛素抵抗和/或隐匿性感染（比如牙周病），羟基喹啉和超敏C反应蛋白水平上升（图2），而这两种物质与全身炎症有关。采用抗炎治疗，包括对于抗坏血酸和镁的补充。JF还通过使用口腔冲洗系统对口腔进行消毒，并且按照医生指示避免糖类和加工过的碳水化合物。处方中有肉桂，这是因为肉桂在降低胰岛素敏感度和抗菌方面具有显著效果。

An elevation of 8-OHdG was discovered (Figure 3). This elevation correlates with DNA oxidative damage. In association with hypertension, nitric oxide is thought to lose its beneficial physiological effects in the presence of oxygen radicals. Therefore, additional vitamin C was given as an antioxidant to address oxidative stress; on follow-up testing, the hsCRP was significantly reduced (Figure 7).

此外，报告还发现8-羟化脱氧鸟苷水平上升（图3）。这与DNA氧化性损伤相关。一氧化氮与高血压有关，但是当氧自由基出现时，一氧化氮会失去它的有益的生理效应，所以，维生素C也被作为抗氧化剂来应对氧化应激。在复查结果中，超敏C反应蛋白明显下降（图7）。

Despite supplementation with magnesium, JF's RBC magnesium level was low (Figure 4). RBC magnesium concentrations significantly lower in hypertensive patients than in controls have been reported.' Additionally, magnesium deficiency has been associated with multiple hypertension-related causes of death .

尽管已经补充了镁，但是JF的红细胞镁水平仍然偏低（图4）。研究显示，高血压患者的红细胞镁浓度明显低于正常人。此外，镁缺乏还与多种与高血压有关的致死原因有关。

Elevated triglycerides and low HDL are indicative of probable insulin resistance despite the normal fasting insulin (Figure 5). The TG/HDL ratio has a high predictive value of a first coronary event regardless of BMLZR The DASH diet, exercise and cinnamon were started to improve insulin sensitivity.

尽管空腹胰岛素水平正常，但增加的甘油三酯和偏低的高密度脂蛋白水平预示可能会出现胰岛素抵抗。DASH型饮食、体育锻炼和肉桂已经开始改善胰岛素敏感度。

JF's elevated coenzymeQ10 and alpha-tocopherol levels (Figure 6) were likely from supplementation, so his vitamin E dosage was decreased. His elevated serum CoQ10 was determined to be advantageous for him. CoQ10 is nontoxic at higher levels, and is beneficial for patients with high 8-OHdG and cardiovascular risks.' Since vitamin E supplementation has had mixed reviews in the literature, it was considered wise to keep that level within normal limits. Figure 6 also shows that his vitamin D level was low.

JF 的CoQ10和α-生育酚的水平上升可能是由于后期补充导致的，所以开始减少维生素E的剂量。CoQ10血清浓度的上升对于JF会产生有利效果，CoQ10在高浓度时是无毒的，而且对于8-羟化脱氧鸟苷水平高并且有心血管疾病风险的患者有益。但在补充维生素E之后，CoQ10的水平最好应控制在正常范围之内。图6显示JF的维生素D水平较低。

CONCLUSION

Hypertension is a worldwide epidemic. The morbidity, mortality and financial cost to society of untreated or undertreated hypertension are remarkably high. Despite this fact, a 2010 report from the Institute of Medicine noted that hypertension is a neglected disease. It is suggested that medication-related side effects are partly responsible.

结论

高血压是一种全球范围内的流行病。经治疗的或未经治疗的高血压的发病率、死亡率和它对社会带来的经济负担都很高。尽管如此，美国医学研究所在2010年的报告显示，高血压是一种被忽视的疾病，造成这种现象的部分原因是由于药物所带来的副作用。

As demonstrated in this case study, however, resistant hypertension was modified using a combination of lifestyle changes and nutrients. Using advanced laboratory analysis to identify the specific factors associated with the patient's hypertension, an effective, individualized plan was designed. The patient was able to lower the dosages of his medications to tolerable, side-effect-free levels. In so doing, he improved his health and well-being, while significantly reducing the risk of recurrence of a hypertensive crisis, congestive heart failure and other associated diseases. Given the dire consequences of hypertension on health, investigation into the efficacy of this safe and effective individualized-plan approach to treatment is warranted.

然而，在本案例中，顽固性高血压通过改变生活方式和补充营养而得到了改善。在使用先进的实验室分析技术确定引起病人高血压的特定因素后，我们就可以为病人量身打造一个有效的医疗计划。病人可以将药物剂量减少到他们可以承受或者没有副作用的程度，这样就可以改善他的身体健康和生活质量，同时还可以降低高血压危象、充血性心力衰竭和其他相关疾病复发的风险。鉴于高血压给健康带来的可怕后果，对于病人安全有效的个人治疗计划功效的研究就显得很有必要。

Vitamin D insufficiency has been associated with hypertension, inflammation and oxidative stress.' Persons with chronic disease are recommended to maintain levels between 55 and 70 ng/mL, as was the goal in this case. The four-month follow-up vitamin D level was 68 ng/mL (Figure 8), right in the target range.

维生素D的缺乏与高血压、炎症和氧化应激有关联。建议慢病患者把维生素D水平维持在55至70ng/mL（这也是在本案例中所要达到的目标）。四个月后的随访显示病人的维生素D水平已经被控制在目标范围内—68ng/mL。

JF initially presented with an elevated blood pressure of 162/104, despite three different antihypertensive medications. He was 30 pounds overweight, under much stress, and he consumed a poor diet. His history included a hypertensive crisis resulting in diastolic dysfunction and congestive heart failure. After four months of treatment using nutrients and diet and lifestyle intervention, his average blood pressure was 135/85. He lost 25 pounds. His medications were reduced: amlodipine and olmesartan medoxomil 20 mg/40 mg to 10 mg/20 mg and carvedilol 40 mg to 12.5 mg. At these amounts, he reported resolution or improvement in all side effects, including ED. It was anticipated that continued adherence to supplement protocol, with adjustments of dosages as needed, and an increasingly vigorous exercise program would further reduce his blood pressure over time.

尽管他服用了三种不同的抗压药物，但是JF最初的血压还是偏高（162/104mmHg）。他当时的饮食习惯很不好，超重30磅，而且感到压力很大。他有高血压危象的病史，还引发了舒张功能障碍和充血性心力衰竭。为期四个月的治疗对他的营养、饮食和生活方式进行了干预，血压被降低至135/85mmHg，体重也减轻了25磅，药物剂量也减少了：氨氯地平和奥美沙坦酯从20mg/40mg减少到10mg/20mg，卡维地洛由40mg减少到12.5mg。在这种剂量之下，所有的副作用都得到了解决或改善，包括勃起功能障碍。可以预见的是，随着时间的推移，在持续性地坚持辅助治疗计划并且逐渐增加运动量的同时，按需要调节药物剂量可以进一步降低患者的血压。

功能医学指导下的高血压干预案例分析（上）

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