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Senior Lecturer in Cardiology, King's College Hospital, Denmark Hill, London SE5, UK

Lecturer in Medicine, King's College Hospital, Denmark Hill, London SE5, UK

1 Many factors are of importance in the relationship between angina pectoris and hypertensive heart disease. Vascular resistance modifies the oxygen supply, whereas the oxygen demand is influenced by the systolic and diastolic BPs, the diastolic filling time and wall tension, the duration of systole and transmural pressure and the sympathetic stimulation to the heart. 2 The treatment of angina pectoris in patients with hypertensive heart disease should aim to reduce myocardial ischaemia, and it is suggested that P-adrenoceptor antagonists are most suitable, as they reduce BP, heart rate and myocardial contractility and thus oxygen demand.

Introduction THE relationship of angina pectoris and hypertensive heart disease is well established (Dawber & Kannel, 1961). Indeed, several studies have shown that although there is an increased risk of death from coronary heart disease, this is not usually reduced by treatment (Hodge & Smirk, 1967; Veterans Administration Cooperative Study Group, 1970, 1972). More recently, however, evidence has been produced to suggest that antihypertensive therapy could at least prevent or postpone coronary heart disease (Berglund et al., 1978). This raises the question as to which drugs might be most effective, and it has been suggested that the P-adrenoceptor antagonists are to be preferred. Fifteen per cent of hypertensive patients have been found to suffer from angina pectoris in our clinic. Coronary arterial disease is the most common cause of death in hypertensive patients with angina but it is possible that factors such as left ventricular hypertrophy play an important role in the patient with hypertensive heart disease (Gordon & Kannel, 1971). It is proposed therefore to examine some of the factors involved and to discuss their relevance and the place of investigation in relation to the subsequent therapy of the hypertensive patient with

hypertensive patient a narrowing of the apparent lumen diameter on coronary arteriography of less than 50%, usually regarded as important, may be sufficient to induce myocardial ischaemia, particularly when left ventricular hypertrophy is present (Davis & Klainer, 1940). The level of the blood pressure is an important determinant of coronary blood flow, particularly when the coronary arteries are diseased and the myocardium hypertrophied. Hypertrophy and alteration of myocardial contractility may be responsible for increased ventricular work, thus increasing oxygen demand (Braunwald, 1969). We should at this point consider those factors that may relate oxygen demand to the supply as determined by the coronary flow. It is evident that apart from those points already mentioned, blood pressure, diastolic filling time, duration of systole, transmural pressure and diastolic ventricular wall tension may all have effects in determining both the myocardial contractility and thus the oxygen requirement and the vascular resistance, which in turn may affect coronary flow and oxygen availability.

Hypertensive heart with hypertrophy

As the state of myocardial metabolism in relation to oxidation depends upon the amount of oxygen coming in (supply) and the amount consumed (demand), either a reduction in supply (as in coronary arterial obstruction) or an increase in demand (as in the hypertrophied ventricle) will result in a shift in the direction of anaerobic metabolism. In addition to hypertrophy, other factors which increase metabolic demands include the increase in the

Ischaemia and myocardial perfusion

Coronary artery disease

The presence of significant coronary arterial stenoses in one or more major coronary arteries may be sufficient to induce ischaemia and thus angina. In the

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Physical Diastolic BP Diastolic filling time Duration of systole Transmural pressure Diastolic wall tension

Figure 1

Factors affecting coronary blood flow.

diastolic and systolic aortic BPs an increase in heart size and the positive inotropic effects of sympathetic stimulation with an increase in heart rate. Elevation of the heart rate is characteristic of hypertension and will augment oxygen demand and the risk of coronary insufficiency (Braunwald, 1969). Myocardial changes of hypertrophy and subsequent failure have been studied in experimental models (Meerson, 1969) and three stages in response to aortic obstruction have been described. In the first stage, activation of protein nucleic acid synthesis leads to the second stage of compensatory hypertrophy, and is followed by the third stage in which the metabolic responses are inadequate with the subsequent development of destructive changes in the myocardial cells, resulting in cardiac failure. A similar pattern of progression may be applicable in the hypertensive heart, and the process of deterioration will be further accelerated when minor degrees of coronary arterial disease are present (Figure 1). In the compensated phase, the need for an increased force of contraction is a stimulus to the hypertrophy, and it has been shown that there is a constant relationship between ventricular wall thickness and the radius of the ventricle in hypertrophy. The thickening of the wall allows a higher systolic BP to be developed without an increase of load in each individual myofibril (Davis & Klainer, 1940). After this phase, however, regional ischaemia may develop with hypertension, as the hypertrophied ventricle becomes stiff, resulting in an increase in the left ventricular end-diastolic filling pressure; the impaired contractility reduces stroke volume. Furthermore, in the phase of hypertrophy with ischaemia the diastolic wall tension may be increased and the left ventricular filling pressure may

rise further leading to reduced perfusion of the subendocardial region, particularly under stress, a disturbance further aggravated by regional changes in contractility. This discussion shows that there is a multifactorial origin for myocardial ischaemia in the hypertrophied heart, and at the present time many of these factors are not completely understood but could have important implications for the possible effects of treatment.

Hypertrophic cardiomyopathy
The similarity of the hypertrophied ventricle in the hypertensive patient to that found in hypertrophic obstructive cardiomyopathy (HOCM) should be mentioned, particularly with regard to the apparent variant of this condition without obstruction. Patients with hypertrophic cardiomyopathy may suffer from angina in the absence of coronary arterial disease (Goodwin & Oakley, 1972). It is interesting that hypertrophic cardiomyopathy may be associated not only with hypertension, but also with valvar aortic stenosis and hyperthyroidism (Symons et al., 1974; Henry et al., 1973) have reported a high incidence of asymmetric hypertrophy (ASH) in the relatives of patients with hypertrophic cardiomyopathy; this disorder has since become increasingly recognized. These subjects are thought by some to show a variant of hypertrophic cardiomyopathy, which is a genetically determined condition, but the finding is not specific. We have found ASH determined on the basis of the echocardiographic finding of a septal to posterior left ventricular wall ratio of greater than 1.5-1.0 (Popp & Harrison, 1969) in a high proportion of patients with hypertension. This subject will be discussed in more detail in the next paper by Hill et al. (1979), who have



Hypertension Increase in left venricular systolic


Increase in myocardial wall tension

Increase in myocardial oxygen demand

Left ventricular hypertrophy

Imbalance between myocardial oxygen demand and supply

Decrease in myocardial contractility

coronary insufficiency

L Heart failure|

Myocardial infarction arrhythmia

Figure 2 Relationship of hypertension to myocardial, ischaemia. (After Hollander, 1976.)

used echocardiography to study the response of the hypertrophied hypertensive left ventricle to 3blockade.

Figure 3 Stages of the hypertensive heart: a, left ventricular hypertrophy + CAD; b, hypertrophic cardiomyopathy; c, late stage congestive.

Investigation of the hypertensive patient with angina Routine chest radiographs, electrocardiograms and echocardiograms are now carried out as a preliminary screening procedure of all our patients who have angina and hypertension. If P-blockade fails to control anginal symptoms the patients are investigated by coronary arteriography and left ventricular angiography. patients. Only three of their patients were studied without treatment. A study by Toshima et al. (1975) on the hypertensive heart has drawn attention to the possibility of asymmetric hypertrophy and hypertrophic cardiomyopathy in hypertensive patients.

M mode echocardiography can now be used to diagnose hypertrophic cardiomyopathy and aortic valve disease. However, its main application in the hypertensive patient has recently been the exclusion of HOCM (Popp & Harrison, 1969); and in the study of left ventricular hypertrophy we have applied the technique to the evaluation of the left ventricular response to antihypertensive therapy (Richardson & Von Bibra, 1978). Karliner et al. (1977) have studied ventricular performance and ventricular wall thickness in the hypertensive patient, but did not note asymmetric septal hypertrophy in treated

Left ventricular angiography and arteriography


In a small series of patients we have studied the left ventricular pattern in patients with angina and hypertension. As one would expect from the experimental studies of Meerson, we have come to recognize three stages (Figure 3): (1) a stage of hypertrophy in which there may or may not be significant coronary arterial disease; (2) a stage of hypertrophy resembling HOCM; (3) the late stage with dilation of the left ventricle showing the features of congestive cardiomyopathy. Angina is infrequent in the latter group (Figure 2).



Angina in hypertensive heart disease can now be seen to be the result of many factors, but perhaps the most important include the systolic and diastolic BPs, the presence of left ventricular hypertrophy, coronary arterial disease and the effects of sympathetic overactivity (de Champlain et al., 1976). Treatment should therefore be aimed at reducing the effects of those factors which are likely to increase myocardial ischaemia. Reduction of the systolic and diastolic arterial BPs is mandatory. By reducing these it is possible that the rate of acceleration of coronary arterial disease may be reduced. Experimentally, left ventricular hypertrophy has seemed to regress following antihypertensive therapy with methyldopa (Sen et al., 1977), and it has now been possible to study these effects clinically using echocardiography (Richardson & Von Bibra, 1978). It is much less certain that the consequence of coronary arterial disease can be altered by therapy, although general measures can be applied, as in the patient with simple coronary artery disease; but perhaps it is more important in this group to reduce sympathetic

overactivity. In this case one of the P-adrenoceptor antagonists, such as propranolol or timolol, may be particularly useful in the treatment of angina in hypertension, as these drugs reduce myocardial oxygen demand not only by lowering BP but also by slowing the heart rate and by decreasing myocardial contractility. Other agents may have similar effects but at the present time it seems more likely that the effects are maximal with the P-blocking drugs. Furthermore, P-blockade has been thought to reduce the incidence of sudden death in patients who have sustained a myocardial infarct (Multicentre International Study Group, 1975), and it is probable that a similar benefit may be seen in the hypertensive patient. At the present time, however, we have no good evidence to support this, although Berglund et al. (1978) have suggested that antihypertensive treatment may have a substantial impact on the incidence of coronary heart disease in the hypertensive patient and that 13-blockade as the treatment for hypertension seems to prevent or at least postpone coronary heart disease.

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AMERINGEN, M. R. (1976). Circulating catecholamine levels in human and experimental hypertension. Circulat. Res., 38, 109-114. GOODWIN, J.F. & OAKLEY, C.M. (1972). The cardiomyopathies. Br. Heart J., 24, 545-552. GORDON, T. & KANNEL, W.B. (1971). Premature mortality from coronary heart disease. JAMA, 215, 1617-1626. HENRY, W.Z., CLARK, C.E. & EPSTEIN, S.E. (1973). Asymmetric septal hypertrophy (ASH): The unifying link in the IHSS disease spectrum. Circulation, 47, 827-832. HILL, L.S., MONAGHAN, M. & RICHARDSON, P.J. (1979). Regression of left ventricular hypertrophy with antihypertensive therapy. Br. J. clin. Pharnac., 7, 255S-260S. HODGE, J.V. & SMIRK, F.M. (1967). The effect of drug treatment of hypertension on the distribution of deaths from various causes. Am. Heart J., 73, 441-452. HOLLANDER, W. (1976). Role of hypertension in atherosclerosis and cardiovascular disease. Am. J. Cardiol., 38, 786-800.

M.H. & O'ROURKE, R.A. (1977). Left ventricular performance in patients with left ventricular hypertrophy caused by systemic arterial hypertension. Br. Heart J., 39, 1239-1245. MEERSON, F.Z. (1969). Myocardium in hyperfunction, hypertrophy and heart failure. Circulat. Res., 25, suppl. II, III-163. MULTICENTRE INTERNATIONAL STUDY GROUP. (1975). Improvement in prognosis of myocardial infarction by long-term P-adrenoceptor blockade using practolol. Br. med. J., 3, 735-740. POPP, R.L. & HARRISON, D.C. (1969). Ultrasound in the diagnosis and evaluation of therapy in idiopathic hypertrophic subaortic stenosis. Circulation, 40, 905-914. RICHARDSON, P.J. & VON BIBRA, H. (1978). Non-invasive evaluation of the acute cardiac effects of methyldopa and propranolol in patients with mild to moderate hypertension. In Methyldopa in Hypertension. Ed. Zanchetti, A. Pp. 127-132. SEN, S., TARAZI, R.C. & BUMPUS, F.M. (1977). Cardiac hypertrophy and anti-hypertensive therapy. Cardiovasc. Res., 11, 427-433. SYMONS, C., RICHARDSON, P.J. & FEIZI, 0. (1974). Hypertrophic cardiomyopathy and hyperthyroidism. Thorax, 29, 713-719. TOSHIMA, H., KOGIA, Y., YOSHIOKA, H., AKIYOSHI, T. & KIMURA, N. (1975). Echocardiographic classification of hypertensive heart disease. Jap. Heart J., 377-393.

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DR HOLLENBERG (Chairman): Two speakers said things that surprised me as a non-cardiologist. First, Dr Richardson, in your use of the Hollander schema there seemed to be an inevitable link between left ventricular hypertrophy and decreased myocardial contractility; and frankly, that arrow surprised me. I didn't realize there was. This statement surprised me.
DR RICHARDSON (London): On the question of myocardial contractility, obviously in the early stages of developing left ventricular hypertrophy, myocardial contractility will be normal; but I think

that in the later stages, after the state of compensatory hypertrophy, there is alteration in the left ventricular myocardial fibers with fibrosis developing; and at this stage, contractility is likely to be reduced and this alteration then imposes its own problems.
DR HOLLENBERG: So it's not hypertrophy per se. DR RICHARDSON: It is the events which in fact surround that and the other alterations that take place at that time.