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 Table of Contents  
GUEST LECTURE
Year : 2016  |  Volume : 13  |  Issue : 1  |  Page : 1-5

Are we close to reclassifying hypertension?


Department of Medicine, Division of Cardiology, University of Ibadan, Ibadan, Oyo State, Nigeria

Date of Web Publication13-Jan-2016

Correspondence Address:
Ayodele O Falase
Department of Medicine, Division of Cardiology, University of Ibadan, Ibadan, Oyo State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0189-7969.173857

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How to cite this article:
Falase AO, Adebiyi AA. Are we close to reclassifying hypertension?. Nig J Cardiol 2016;13:1-5

How to cite this URL:
Falase AO, Adebiyi AA. Are we close to reclassifying hypertension?. Nig J Cardiol [serial online] 2016 [cited 2019 Dec 13];13:1-5. Available from: http://www.nigjcardiol.org/text.asp?2016/13/1/1/173857

THE 2015 NIGERIAN CARDIAC SOCIETY ANNUAL ASUQUO ANTIA LECTURE


  Historical Perspectives Top


The typical pattern of heart failure (HF) in a black African hospital several years ago is shown in [Figure 1].[1] From this figure, it was obvious that the most common cause of HF among Africans was hypertension followed by a disease labeled myocardial disease in the figure.
Figure 1: Causes of heart failure in Nigerians at the University College Hospital, Ibadan, between 1968 and 1969 (Carlisle and Ogunlesi)

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Myocardial diseases were obscure forms of heart disease which primarily affected the heart muscle. Initial descriptions of such diseases came from Africa and they were published under various names – idiopathic cardiomegaly, nutritional heart disease, cardiovascular collagenosis with parietal endocardial thrombosis, cardiomyopathy, idiopathic hypertrophy of the heart, cryptogenic heart disease, heart muscle disease, cardiac disorder of unknown etiology, and congestive cardiomyopathy.[2] A universal name “cardiomyopathy” was adopted at a World Health Organisation/International Society and Federation of Cardiology sponsored meeting for such diseases in 1980.[3]

Studies in Nigeria over the years have, however, shown that majority of patients diagnosed as having myocardial diseases were in fact hypertensives with varying degrees of left ventricular (LV) dysfunction.[2],[4] It thus became obvious to clinicians working in Nigeria and indeed other African countries that the burden of hypertension in Africa was higher than originally estimated, while that of ischemic heart disease (IHDX), which was and is still the most common form of heart disease in advanced countries of the world, was low.

Recently, Ogah et al.[5] compared the causes of HF at the University College Hospital, Ibadan, Nigeria, in 1968 with that of 2010 and it showed clearly that the burden of hypertension has increased phenomenally in Nigeria [Figure 2]. In fact, it has become an epidemic.
Figure 2: Causes of heart failure in Nigerians at the University College Hospital, Ibadan, between 1968 and 1969 (Carlisle and Ogunlesi, 1972) compared with causes of heart failure in the same ethnic group in the year 2010. HHF – Hypertensive heart failure; RHDX – Rheumatic heart disease; DCM – Dilated cardiomyopathy; EMF – Endomyocardial fibrosis; CP – Cor pulmonale; IHDX – Ischemic heart disease

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The study also showed that the prevalence of rheumatic heart disease had decreased considerably, while endomyocardial fibrosis, which was common in 1968, had virtually disappeared. The prevalence of IHDX, though still low, had increased.

Studies within the same population of hypertensives also showed that the myocardial response to hypertension in the community began with concentric hypertrophy or asymmetric septal hypertrophy.[6],[7],[8],[9],[10] If hypertension remained uncontrolled, there was progression of myocardial disease beginning with dilatation of the LV cavity to the stage of eccentric hypertrophy by which time the patient is in advanced HF, sometimes in cardiogenic shock [Figure 3].[7]
Figure 3: Representation of progression of the left ventricle in hypertensives from concentric hypertrophy with small cavity through concentric hypertrophy with large cavity to a destroyed myocardium unable to sustain a high blood pressure

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Studies also showed that the genesis of HF was as follows:

  • Early hypertension was characterized by elevated cardiac output (CO)/index with a mild rise in systemic vascular resistance (SVR)[6],[11]
  • As hypertension became more severe, CO/index floated back to normal whereas the SVR continued to rise [11],[12]
  • If hypertension still remained uncontrolled, deterioration of LV function with reduction of CO/index may begin despite the presence of high SVR leading to the rapid development of HF.[2],[4],[7],[11] Lack or ineffective control of high blood pressure was therefore the major cause of hypertensive HF in Nigeria and this could be stemmed by better control of high blood pressure. Contributory factors include excessive intake of alcohol, myocarditis, anemia, and high parity in women.[11],[13]


Hormonal profile of patients with hypertension

Initial assays of the hormonal changes which occurred in patients with primary hypertension without HF compared with normal patients showed the following results:[4]

  • Plasma sodium – lower;
  • Urinary sodium excretion – increased;
  • Plasma potassium – lower;
  • Urinary potassium excretion – lower;
  • Plasma renin activity – lower;
  • Plasma aldosterone – elevated;
  • Plasma volume – contracted;
  • Plasma cortisol – normal;
  • Urinary excretion of vanillylmandelic acid (VMA) – increased.


With the onset of HF,
  • Serum Na +/K + – became lower;
  • Plasma renin activity – remained low;
  • Serum aldosterone – became more elevated;
  • Plasma cortisol – also rose to higher levels;
  • Plasma volume – increased;
  • Urinary potassium excretion – decreased;
  • Urinary sodium excretion – reduced significantly;
  • Urinary VMA excretion – showed no difference.


The significance of these biochemical results in hypertensives without HF was however baffling, especially as it related to aldosterone. Excretion of sodium was found to be higher in hypertensives despite a high level of aldosterone. Moreover, despite a high level of aldosterone, plasma renin level was low; plasma volume too was contracted, and plasma sodium was lower compared with normals. All these were contrary to what was expected if the serum aldosterone level was genuinely high. Urinary level of VMA was, however, observed to be high in all the patients whether they were in HF or not. Serum adrenaline and noradrenaline levels could not be separately measured at the time.

The changes that occurred after the onset of HF were however easier to interpret as they were in accordance, with the changes that normally occurred when any patient is in HF.


  Comparison between Hypertension in Blacks and Whites Top


A comparison between black and white hypertensives provided a good insight into the peculiar nature of Nigerian/black hypertensives and this was as shown in [Table 1].[12],[14],[15]
Table 1: Peculiarities of hypertension in Africans

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Ogah et al.[16] recently did an interesting review of all the scientific publications on hypertension emanating from Nigeria. Of the papers which examined the pathophysiology of the disease, the most promising was the work of Adebiyi et al.[17] This shall be further examined in the discourse that follows as it has implications on the genesis of hypertension.

Recent studies on the hormonal profile of Nigerian hypertensives

Adebiyi et al.[17] performed a more comprehensive study on the hormonal profile of Nigerian hypertensives in view of the previous inadequacies observed earlier. Compared with earlier studies, their study was much more detailed and precise. It involved a larger number of patients and the authors used more accurate and modern biochemical assay techniques. Their results can be abridged as follows:

  • Serum sodium – same as in the earlier study; serum sodium was lower in hypertensives; the difference was however not statistically significant;
  • Serum potassium – same as in the earlier study, serum potassium was lower in hypertensives; the difference was similarly not statistically significant;
  • Serum creatinine – this was found to be higher in hypertensives but the level was not statistically significant;
  • Urinary sodium – same as in the earlier study, the level of urinary sodium was higher in hypertensives although the difference was not significant;
  • Urinary sodium excretion – again, same as in the earlier study, this was higher in hypertensives but the difference was not statistically significant;
  • Urinary potassium excretion – was similar to urinary sodium excretion. Similar to the earlier study, this was higher in hypertensives but the difference was not statistically significant;
  • Urinary potassium – was similar to sodium; it was higher in hypertensives;
  • Urinary creatinine – higher in hypertensives;
  • Plasma renin – same as in the earlier study, this was significantly lower in hypertensives;
  • Plasma angiotensin converting enzyme (ACE) – significantly lower in hypertensives;
  • Plasma atrial natriuretic peptide – significantly lower in hypertensives;
  • Plasma aldosterone – same values as controls were obtained;
  • Plasma adrenaline – significantly lower in hypertensives;
  • Plasma noradrenaline – significantly higher in hypertensives;
  • Urinary VMA – lower in hypertensives; not statistically significant;
  • Plasma insulin – lower in hypertensives; not statistically significant;
  • Fasting plasma glucose – slightly higher in hypertensives; not statistically significant.


The conclusions that can be drawn from this study are as follows:

  • Although the values were not statistically different from the controls, there was a tendency for Nigerian hypertensives to excrete more sodium and potassium in their urine compared with normal individuals. This was similar to the findings in previous studies. Serum sodium levels also tended to be lower in both studies
  • The same findings were observed with serum and urinary potassium levels. This raised the question of the appropriateness of restricting salt intake in hypertensive patients as currently practiced. Moreover, it raised the question of whether this finding represented the beginning of renal disease in hypertensives. The much-touted association between hypertension and salt intake has recently been questioned,[18] and a good summary of salt intake and disease can be found in a recent paper by Agarwal [19]
  • The renin–angiotensin–aldosterone system was dormant in the hypertensive patients. So also was the atrial natriuretic peptide system, perhaps because the atria of the patients were yet to dilate. Adebiyi et al., further examined the relationship between plasma aldosterone and LV mass in a subsequent paper and found none.[20] LV mass was more related to the height of blood pressure and the age of the patient [20]
  • The tendency toward lower levels of plasma insulin level was intriguing. Perhaps, this was an early sign of damage to the insulin-producing areas of the pancreas
  • The most interesting finding was the significant elevation of plasma noradrenaline in the patients compared with controls. Paradoxically, plasma adrenaline was significantly reduced in the patients compared with controls. Adebiyi et al., rightly believed that these results showed the presence of a chronic hyperadrenergic state in hypertensives.[17] According to Adebiyi et al., “The results of this study supported the hypothesis that activation of the sympathoadrenergic system might play a dominant role in the genesis of hypertension. Several methods have been developed in the evaluation of the adrenergic system in hypertension and these have ranged from the measurement of the plasma levels of catecholamines to the direct assessment of human sympathetic function with methods such as noradrenaline radiolabeled spillover technique, the microneurographic recording of efferent postganglionic muscle sympathetic nerve firing rate, and power spectral analysis of heart rate signal. These studies have provided evidence that suggests that sympathetic overdrive is a hallmark of hypertension of essential nature”[17]
  • The authors also believed that reduction of plasma adrenaline level and its negative correlation with the blood pressure probably indicated suppression of production of catecholamines by the adrenal glands in response to high circulating plasma noradrenaline [17]
  • Finally they believed that the metabolic disarray frequently observed in primary hypertensives is due to sympathetic overdrive and that the “lower renin, angiotensin converting enzyme, and atrial natriuretic peptide levels observed in this study could be as a result of a negative feedback mechanism from the heightened adrenergic activity suppressing other counter-regulatory hormones.”[17]


Stress and hypertension

Noradrenaline is a neurotransmitter which causes tachycardia. It is also a stress hormone and is involved in the flight-or-fight response of the body,[21] since stress increases the amount of noradrenaline secreted relative to adrenaline.[22] It is possible to reach a conclusion from this study that primary hypertension is most likely related to stress. The original observation of populations moving from a basic rural observation where there was no single case of hypertension to urban areas where they developed hypertension, was therefore most likely related to stress and a heightened, chronic adrenergic state than increased salt intake.[23] Similarly, a recent study suggests that chronic stress could play a key role in the racial/ethnic disparities in the prevalence of hypertension among blacks and whites in the United States.[24] Our clinical observations would tend to support this assertion.

Clinical observations

A patient had complaints of palpitations, insomnia, and restlessness. He had sinus tachycardia as shown in the electrocardiogram and he was found to be hypertensive. He responded to a combination of atenolol, ramipril, and amlodipine. It was believed that his tachycardia was due to a hyperadrenergic state as there was no other plausible explanation. The second case was that of a banker who was known to be hypertensive, but his blood pressure was difficult to control. He was taking high doses of valsartan, atenolol, and amlodipine to control his high blood pressure. He too had insomnia in addition to angina pains and acid-peptic disease. During follow-up, he developed type 2 diabetes mellitus which responded to oral hypoglycemic agents. After he retired from his stressful job, his ulcer symptoms became easier to manage and he was no longer using medication for it. Moreover, he slept better although he still had type 2 diabetes mellitus. He no longer had anginal pains and his antihypertensive drugs had to be scaled down because of postural hypotension.

The concept of two stages in the development of hypertension

Previous hemodynamic studies did suggest that the early stage of primary hypertension was characterized by elevated CO and normal SVR. Many of the patients often present at this stage with palpitations and sinus tachycardia. During the late stages however, the CO often normalizes whereas the SVR rises.[4] This is the stage when majority of the patients present to clinicians with hypertension.

The implication of these hemodynamic changes is that there are possibly two stages in the development of hypertension – the induction stage and the stage of perpetuation. It also suggests that irrespective of the mechanism responsible for inducement of hypertension, perpetuation of hypertension in the long term is due to a chronic rise in SVR. In other words, perpetuation of hypertension is due to endothelial changes which include thickening and diminished ability of the resistance vessels to distend. These arose as a reaction of the vasculature to high pressure within the arterial vasculature.

Other inducers

The inducer of primary hypertension seems to be a chronic hyperadrenergic state epitomized by the significant elevation of plasma noradrenaline in our patients. However, there are other well-known inducers. For example, aldosterone tumor/hyperplasia is known to induce hypertension through sodium retention (Conn's syndrome), whereas adrenal medulla tumors are known to induce hypertension through massive production of catecholamine (phaeochromocytoma). Overproduction of glucocorticoids in Cushing's disease and Cushing's syndrome causes sodium retention and hypertension.

Implication of the two stages in the development of hypertension

The implication of this is that the dividing line between primary/essential hypertension and secondary hypertension is becoming blurred and this may require a reclassification of hypertension in the nearest future. There may be other inducers of hypertension yet to be identified, but if the ultimate aim is to prevent hypertension from developing, this is the area all clinicians and researchers should now focus on.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Carlisle R, Ogunlesi TO. Prospective study of adult cases presenting at the cardiac unit, university college hospital, Ibadan 1968 and 1969. Afr J Med Sci 1972;3:13-25.  Back to cited text no. 1
    
2.
Falase AO, Ogah OS. Cardiomyopathies and myocardial disorders in Africa: Present status and the way forward. Cardiovasc J Afr 2012;23:552-62.  Back to cited text no. 2
    
3.
Report of the WHO/ISFC task force on the definition and classification of cardiomyopathies. Br Heart J 1980;44:672-3.  Back to cited text no. 3
    
4.
Lawal SO, Osotimehin BO, Falase AO. Mild hypertension in patients with suspected dilated cardiomyopathy: Cause or consequence? Afr J Med Med Sci 1988;17:101-12.  Back to cited text no. 4
    
5.
Ogah OS, Adebiyi AA, Oladapo OO, Adeoye MA, Adekunle AN, Oyebowale OM, et al. The changing patterns of heart disease in Nigeria: Data from the Ibadan outpatient cardiac registry. Circulation 2012;125:e679.  Back to cited text no. 5
    
6.
Lawal SO, Falase AO. The effect of hypertension on the heart of adult Nigerians. Trop Cardiol 1988;14:153-9.  Back to cited text no. 6
    
7.
Aje A, Adebiyi AA, Falase AO. Hypertensive heart disease in Africa: Hypertensive heart disease. SA Heart 2009;6:42-51.  Back to cited text no. 7
    
8.
Aje A, Adebiyi AA, Oladapo OO, Dada A, Ogah OS, Ojji DB, et al. Left ventricular geometric patterns in newly presenting Nigerian hypertensives: An echocardiographic study. BMC Cardiovasc Disord 2006;6:4.  Back to cited text no. 8
    
9.
Adebiyi AA, Ogah OS, Aje A, Ojji DB, Adebayo AK, Oladapo OO, et al. Echocardiographic partition values and prevalence of left ventricular hypertrophy in hypertensive Nigerians. BMC Med Imaging 2006;6:10.  Back to cited text no. 9
    
10.
Ogah OS, Sliwa K, Akinyemi JO, Falase AO, Stewart S. Hypertensive heart failure in Nigerian Africans: Insights from the Abeokuta Heart Failure Registry. J Clin Hypertens (Greenwich) 2015;17:263-72.  Back to cited text no. 10
    
11.
Falase AO. Cardiomegaly of unknown origin among Nigerian adults: Role of hypertension in its aetiology. Br Heart J 1977;39:671-9.  Back to cited text no. 11
    
12.
Falase AO. Are there differences in the clinical pattern of hypertension between Africans and Caucasians? In: Control of hypertension in developing countries with special reference to Africa. Trop Cardiol 1987;(Supl 13):141-50.  Back to cited text no. 12
    
13.
Falase AO, Ayeni O, Sekoni GA, Odia OJ. Heart failure in Nigerian hypertensives. Afr J Med Med Sci 1983;12:7-15.  Back to cited text no. 13
    
14.
Ogunlesi AO, Akinkugbe OO. Hypertension, in black and white. Lancet 1992;339:680-1.  Back to cited text no. 14
    
15.
Akinkugbe OO. High blood pressure in the African context. Trop Doct 1980;10:56-8.  Back to cited text no. 15
    
16.
Ogah OS, Okpechi I, Chukwuonye II, Akinyemi JO, Onwubere BJ, Falase AO, et al. Blood pressure, prevalence of hypertension and hypertension related complications in Nigerian Africans: A review. World J Cardiol 2012;4:327-40.  Back to cited text no. 16
    
17.
Adebiyi AA, Akinosun OM, Nwafor CE, Falase AO. Plasma catecholamines in Nigerians with primary hypertension. Ethn Dis 2011;21:158-62.  Back to cited text no. 17
    
18.
Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, et al. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA 2011;305:1777-85.  Back to cited text no. 18
    
19.
Agarwal SK. Salt intake: Cardiovascular concerns and controversies. Disease 2015;7:1-5.  Back to cited text no. 19
    
20.
Nwafor CE, Adebiyi AA, Ogah OS, Falase AO. Relationship between 24-hour blood pressure pattern and left ventricular structure and function in hypertensive Nigerians. Ethn Dis 2013;23:474-9.  Back to cited text no. 20
    
21.
Ganong WF, Barrett KE. Review of Medical Physiology. New York: McGraw-Hill Medical; 2005.  Back to cited text no. 21
    
22.
Oyebola DO. Essential Physiology. Ibadan: NIHORT Press; 2002.  Back to cited text no. 22
    
23.
Poulter NR, Khaw KT, Hopwood BE, Mugambi M, Peart WS, Rose G, et al. The Kenyan Luo migration study: Observations on the initiation of a rise in blood pressure. BMJ 1990;300:967-72.  Back to cited text no. 23
    
24.
Tanaka M, Yoshida M, Emoto H, Ishii H. Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: Basic studies. Eur J Pharmacol 2000;405:397-406.  Back to cited text no. 24
    


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