Hypertension: A Symptom, Not A Disease

Tolle Causam

Hypertension is regularly mismanaged in conventional and naturopathic medicine. The tyranny of the concept of “essential hypertension,” coupled with the widespread tendency to treat hypertension as a disease rather than a symptom, is at the root of this problem. Here, a more holistic approach to the patient with elevated blood pressure will be promoted, primarily one that attempts to find the causes of the problem rather than just treating the symptom.

The Essential Hypertension Myth

The conception of blood pressure began, in part, with the first full description of circulation of blood by the English physician William Harvey (1578-1657). The first published measurement of blood pressure is believed to have been made by the English priest Stephen Hales (1677-1761) in 1733. Though a clear conception that very high (so-called “malignant”) hypertension could cause death within a few years emerged in the 1920s, milder hypertension was considered unnecessary to treat until the 1950s.^1,2

The phrase “essential hypertension,” meaning a state of elevated blood pressure for which no cause can be found, was apparently coined by the German physician Eberhard Frank (no dates found) in 1911.³ This was used to describe hypertension not clearly due to severe renal disease, and without any other other obvious or simple cause. Today, unfortunately, many practitioners that detect persistently elevated blood pressure readings diagnose “essential hypertension” (despite no or minimal work-up to rule out causes of the disease) and prescribe antihypertensive medications. This approach has become dominant, in part, because it does dramatically reduce cardiovascular mortality.^4,5 However, this approach does not always work (as evidenced by so-called “resistant hypertension,” most likely due to using drugs that don’t treat the cause and thus don’t control the blood pressure) and it ensures a lifetime of medication with potential adverse effects.

But hypertension does have underlying causes and is not a simple genetic trait or an unsolveable mystery. It is imperative that the cause of the symptom of hypertension be identified (where possible) to allow for curative therapy, or likely risk factors modified to avoid a lifetime of increasing medication and the possible development of other diseases when these risk factors are not eliminated. For instance, although blood pressure may be controlled by medication, a patient may nonetheless develop type 2 diabetes mellitus due to underlying insulin resistance that antihypertensives do not address. Note that I am not arguing that persistently elevated blood pressure should not be controlled by natural or pharmaceutical means, only that this approach is neither sufficient nor optimal in many cases.

Intial Hypertension Work-Up

Numerous identifiable and treatable (potentially curable) causes of hypertension are well documented (see Table 1). Unfortunately, it is all too common that there is little or no work-up when a middle-aged patient is diagnosed with hypertension. History-taking should cover risks, signs, and symptoms for all identifiable causes of hypertension. The most basic work-up includes a complete blood count, fasting lipid profile, and basic serum chemistries (assessing, at a minimum, fasting serum glucose, serum creatinine, estimated glomerular filtration rate, serum potassium, and serum calcium). Spot or 24-hour urine protein testing (so-called microalbumin testing) is also recommended, as it is a better predictor of cardiovascular outcomes than lipid levels and is an earlier marker of kidney disease than serum creatinine.⁶ Serum C-reactive protein is also helpful to assess for systemic inflammation.

Table 1. Identifiable Causes of Hypertension⁷

Sleep apnea

Chronic kidney disease

Drug-induced:Nonsteroidal anti-inflammatory drugs8 Cyclooxygenase-2 inhibitors Amphetamines (including treatment for attention deficient disorder) Glucocorticoids Sympathomimetics (decongestants, anorectics) Oral contraceptive hormones Cyclosporine Tacrolimus Erythropoietin Glycyrrhiza spp; chronic overdose Ephedra sinica and ephedrine alkaloids; chronic overdose Cocaine

Primary aldosteronism and other states of mineralocorticoid excess

Obstructive uropathy

Cushing syndrome and other states of glucocorticoid excess, including chronic steroid therapy

Thyroid or parathyroid disease

Renovascular hypertension

Coarctation of the aorta

Pheochromocytoma

Note: These are listed roughly in order of frequency at which they occur. It must also be emphasized that reasonable doses of Glycyrrhiza spp (licorice) do not cause hypertension, particularly when coupled with a high-potassium diet, thus do not need to be avoided by all hypertensive patients. The only published cases of licorice-induced hypertension have involved people eating excessive amounts of true licorice-flavored candy abroad; licorice candy in the United States is flavored with anise and contains no true licorice. (Table modified from Chobanian et al, 2003⁷)

Patients’ cardiovascular risk factors must be assessed in depth, as these risk factors are generally associated with hypertension. Adiposity, sleep apnea, dyslipidemia, insulin resistance, and systemic inflammation should all be considered in this work-up. Patients with these risk factors should, of course, be treated for them, preferably with lifestyle changes, though some supplements or medications may also be needed in some cases.

Patients with so-called “resistant” hypertension (non-responsive to 3 or more antihypertensive drugs of different classes) should also be assessed for the problems listed in Table 1, if they haven’t been already.

Hyperaldosteronism: Not Rare, Just Rarely Noted

One of the highest-yield early investigations undertaken in patients with hypertension involved Conn’s syndrome, or primary hyperaldosteronism. Originally identified by American endocrinologist Jerome Conn (1907-1994), this syndrome was long believed to be rare or uncommon, partly due to poor-quality tests for aldosterone levels and partly due to the misperception that all patients with this syndrome should be hypokalemic. However, the advent of accurate aldosterone tests and the realization that only the most severe patients with primary hyperaldosteronism have hypokalemia has led to a clear recognition that 5-13% of all hypertensive patients in multiple racial groups have this condition.⁹

The key to diagnosing primary hyperaldosteronism, which often causes the sole symptom of hypertension, is to run an aldosterone-to-renin activity ratio (ARR) test in all patients that present with high blood pressure of no discernable cause.¹⁰ Interpretation of this test is reviewed in Table 2.

Table 2. Aldosterone-Renin Activity Ratio Interpretation

Condition	Plasma Aldosterone, upright*	Plasma Renin Activity, upright*	Aldosterone:Renin Activity Ratio
Primary hyperaldosteronism	<15 ng/dL(≤416 pmol/L)	<1 ng/mL/h**	≥20 ng/dL/ng/mL/h (≥555 pmol/L/ng/mL/h)
Primary hyperaldosteronism on ACEi, ARB, or thiazide	Any (usually <15 ng/dL)	Undetectable	Any
Secondary hyperaldosteronism	>31 ng/dL(>860 pmol/L)	>1 ng/mL/h	<10 ng/dL/ng/mL/h (<277 pmol/L/ng/mL/h)

*All values assume the patient is upright (not supine) during testing. All criteria must be met to do further work-up for a form of hyperaldosterism.

** (Or plasma renin concentration below the threshold of detection for the assay)

(ACEi = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker)

These tests must be conducted between 8-10 AM, with the patient seated or standing for accurate results and having been ambulatory for at least 30 minutes prior to the blood draw. Frankly hypokalemic patients should be restored to normokalemia before performing the tests. The patient cannot have taken spironolactone (or other aldosterone receptor antagonists) or high-dose amiloride for the past 6 weeks, as they will invalidate the results. Though stopping any other drugs that affect renin activity, such as angiotensin-converting enzyme inhibitors (ACEi), angiotension receptor blockers (ARB), or thiazide diuretics for 6 weeks before the test will also result in the clearest results, a completely undetectable plasma renin activity while taking such drugs strongly suggests primary hyperaldosteronism, regardless of plasma aldosterone level and ARR. Some have therefore argued that these drugs do not have to be stopped to interpret ARR testing.¹¹ Results that suggest primary hyperaldosteronism require referral to an endocrinologist for further testing, including adrenal imaging to locate an aldosterone-secreting adenoma and various confirmatory suppression tests. Causes of secondary hyperaldosteronism, notably congestive heart failure, dehydration, severe renal artery stenosis, and hepatic cirrhosis, should be identified and treated if lab findings suggest that the syndrome is present.

Determining plasma renin activity has a side benefit of detecting salt-sensitive patients, obviating the need for everyone to follow a low-salt diet when only a portion of the population actually benefits from this. In the presence of normal serum aldosterone and ARR, plasma renin activity <0.65 ng/mL/h suggests that the patient is salt-sensitive.¹² This is significantly more common in African-American and Hispanic patients, affecting up to 66% of these groups, as compared to just 33% in non-Hispanic European-Americans.¹³ Patients with this finding may have dramatic blood pressure improvements on a low-salt/high-potassium diet; those without the finding are unlikely to respond. Patients with plasma renin activity ≥0.65 ng/mL/h, in the absence of hyperaldosteronism, usually have systemic inflammatory/vasoconstrictive hypertension.

Individualizing Treatment

The approach described here facilitates individualized treatment instead of simplistic antihypertensive drug prescribing. A summary of the major individualized types of treatment, based on what is driving the symptom of hypertension in any patient, is provided in Table 3. It must also be emphasized that all treatment guidelines involving hypertension recommend that lifestyle approaches to treatment be tried before drug treatment.¹⁴

Table 3. Individualized Treatment of Hypertension

Problem	Treatment
Primary hyperaldosteronism due to aldosterone-secreting adenoma	Surgical removal of adenoma if possible, spironolactone if not*
Primary hyperaldosteronism due to bilateral adrenal hyperplasia	Spironolactone*
Drug-induced hypertension	Removal of causative drug
Sleep apnea-associated hypertension	Decrease adiposity via lifestyle changes; positive airway pressure devices
Chronic kidney disease-associated hypertension	Identify and treat cause of CKD if possible; nephroprotective herbs, renal adaptogens, Rauvolfia serpentina (Indian snakeroot) with or without ACEi or ARB if progressive
Salt sensitivity (low-renin hypertension)	Low-sodium, high-potassium diet, herbal diuretics, high water intake, thiazide diuretic or calcium channel-blocker if necessary
Systemic inflammatory/vasoconstrictive hypertension (high-renin hypertension)	Anti-inflammatory diet rich in fruits and vegetables, increased omega-3 essential fatty acids, dietary Curcuma longa (turmeric), beta-blocker, ACEi, or ARB if necessary
Other causes (hyperthyroidism, obstructive uropathy, Cushing’s syndrome, etc)	Treat underlying cause; use Rauvolfia serpentina or antihypertensive drugs as needed to control blood pressure temporarily
Metabolic hypertension, pre-diabetes, and similar insulin-resistant states	Reduce adiposity, increase fruit and vegetable intake, avoid processed carbohydrates, exercise regularly

* There are no known natural aldosterone antagonists

(ACEi = angiogensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CKD = chronic kidney disease)

Closing Comments

Many practitioners understandably become nervous when patients present with malignant hypertension (blood pressure ≥180/120 mm Hg), but tend to overreact. If the patient has no evidence of end-organ damage (eg, papilledema, hematura, proteinuria, chest pain, vomiting or other signs of increased cranial pressure, or intracranial bleeding) in the presence of such high blood pressures, there is no need to intervene drastically to force the blood pressure down.¹⁵ In fact, using intravenous sodium nitroprusside or other aggressive measures to rapidly lower blood pressure in severe, asymptomatic hypertension has been shown to cause just as many problems as it helps.¹⁶

So, it is completely reasonable to do the same work-up but with initiation of some therapies (be they herbs or drugs) that will bring down blood pressure levels within 48 hours (for patients with other significant cardiovascular risk factors) or within a few weeks (for those without). Only patients with true hypertensive emergencies (malignant hypertension coupled with signs of end-organ damage) should be referred to the emergency room for immediate blood pressure lowering and continual monitoring.

References:

1. Keith NM, Wagener HP, Kernohan JW. The syndrome of malignant hypertension. Arch Intern Med. 1928;41(2):141-188.
2. Pickering GW. The natural history of hypertension. Br Med Bull. 1952;8(4):305-309.
3. Frank E. Relationships between the chromaffin system and the chronic hypertension of humans? Dtsch Arch Klin Med. 1911;103:397-412. [Article in German]
4. Kotchen TA. Historical trends and milestones in hypertension research: a model of the process of translational research. Hypertension. 2011;58(4):522-538.
5. Dustan HP, Roccella EJ, Garrison HH. Controlling hypertension. A research success story. Arch Intern Med. 1996;156(17):1926-1935.
6. Wu CK, Chang MH, Lin JW, et al. Renal-related biomarkers and long-term mortality in the US subjects with different coronary risks. Atherosclerosis. 2011;216(1):226-236.
7. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42(6):1206-1252.
8. Varga Z, Sabzwari SRA, Vargova V. Cardiovascular risk of nonsteroidal anti-inflammatory drugs: an under-recognized public health issue. Cureus. 2017;9(4):e1144.
9. Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol. 2007;66(5):607-618.
10. Montori VM, Young WF Jr. Use of plasma aldosterone concentration-to-plasma renin activity ratio as a screening test for primary aldosteronism. A systematic review of the literature. Endocrinol Metab Clin North Amer. 2002;31(3):619-632.
11. Seifarth C, Trenkel S, Schobel H, et al. Influence of antihypertensive medication on aldosterone and renin concentration in the differential diagnosis of essential hypertension and primary aldosteronism. Clin Endocrinol (Oxf). 2002;57(4):457-465.
12. Laragh J. Laragh’s lessons in pathophysiology and clinical pearls for treating hypertension. Am J Hypertens. 2001;14(5 Pt 1):397-404.
13. Richardson SI, Freedman BI, Ellison DH, Rodriguez CJ. Salt sensitivity: a review with a focus on non-Hispanic blacks and Hispanics. J Am Soc Hypertens. 2013;7(2):170-179.
14. Eckel RH, Jakicic JM, Ard JD, et al. AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129(25 Suppl 2):S76-S99.
15. Kessler CS, Joudeh Y. Evaluation and treatment of severe asymptomatic hypertension. Am Fam Physician. 2010;81(4):470-476.
16. Decker WW, Godwin SA, Hess EP, et al. Clinical policy: critical issues in the evaluation and man- agement of adult patients with asymptomatic hypertension in the emergency department. Ann Emerg Med. 2006;47(3):237-249.

 

This article was originally published by Naturopathic Doctor News & Review.