Hypertension and coronary heart disease

Abstract

The association of hypertension and coronary heart disease is a frequent one. There are several pathophysiologic mechanisms which link both diseases. Hypertension induces endothelial dysfunction, exacerbates the atherosclerotic process and it contributes to make the atherosclerotic plaque more unstable. Left ventricular hypertrophy, which is the usual complication of hypertension, promotes a decrease of ‘coronary reserve’ and increases myocardial oxygen demand, both mechanisms contributing to myocardial ischaemia. From a clinical point of view hypertensive patients should have a complete evaluation of risk factors for atherosclerosis, damage of arterial territories other than the coronary one, and of the extension and severity of coronary artery involvement. It is important to emphasise that complications and mortality of patients suffering a myocardial infarction are greater in hypertensive patients. Treatment should be aimed to achieve optimal values of blood pressure, and all the strategies to treat coronary heart disease should be considered on an individual basis.

Main

There is a strong and frequent association between arterial hypertension and coronary heart disease (CHD). In the PROCAM study, in men between 40 and 66 years of age, the prevalence of hypertension in patients who had a myocardial infarction was 14/1000 men in a follow-up of 4 years. This figure increased to 48 when hypertension was associated to diabetes mellitus and 114 when it was associated to diabetes and hyperlipidaemia.1 Major secondary prevention trials with statins (4S, CARE and LIPID), included patients with myocardial infarction and angina pectoris. If baseline characteristics of these trials are analysed it is observed that patients in the 4S study had hypertension in 26% of the cases,2 and patients in the CARE3 and LIPID4 studies had 43% and 41% incidence of hypertension respectively. On the other hand the mortality rate of CHD is 2.3 times greater when hypertension is present.5

There is no doubt that the magnitude of hypertension does have an impact in the incidence of CHD. If the risk ratio is 1 for a diastolic pressure <80 mm Hg, this ratio increases progressively when diastolic pressure is higher, and at least duplicates at values of 94 mm Hg or more.6

Risk ratio for myocardial infarction is 1 when systolic pressure is between 120 and 129 mm Hg, and almost 2 when this value is greater than 140 mm Hg.7 There are important pathophysiologic links between arterial hypertension and CHD which might explain the pathogenenesis of CHD when hypertension is present.

First of all, atherosclerosis is exacerbated by arterial hypertension.8 Hypertension is frequently associated to metabolic disorders, such as insulin resistance with hyperinsulinaemia and dyslipidaemia, which are additional risk factors of atherosclerosis.9

Deposition of lipids and the formation of the atherosclerotic plaque may be favoured by the increase of transmural pressure in arterial vessels, with an increase in mechanical stress and endothelial permeability. Furthermore, it is well documented that there is endothelial dysfunction, remodelling of coronary arteries and increased resistance at microvascular level, all contributing to a decrease of coronary reserve.10

Coronary reserve is impaired in patients with essential arterial hypertension in the absence of CHD,10 which is explained in part by the presence of left ventricular hypertrophy. Experimental studies have shown that minimal coronary resistance is increased in spontaneous hypertensive rats, along with a decrease in capillary density and coronary reserve.11

In dogs with chronic renovascular hypertension and left ventricular hypertrophy it has been shown that the wall/lumen ratio is not significantly increased in arterioles and arteries of different sizes, compared with normotensive animals. An increase in the wall/lumen ratio would not explain the increased vascular resistance.12 This increased resistance has been confirmed in patients; flow is also increased along with a significant increase of myocardial oxygen consumption.13

It has been recently confirmed that coronary blood flow is increased in hypertensive patients with left ventricular hypertrophy compared with hypertensives without hypertrophy and normotensives.

The lumen area was similar in hypertensives with hypertrophy of the left ventricle and normotensives, and significantly greater than hypertensives without hypertrophy. Vessel area was significantly greater in hypertensives with hypertrophy than in those without. Vessel area increased significantly with plaque area in the three groups. On the other hand responses to acetilcholine (endothelium dependent) and to adenosine (non-endothelial dependent) are significantly decreased in patients with left ventricular hypertrophy.14

These results suggest that functional abnormalities in humans with hypertension and left ventricular hypertrophy are associated with structural changes, namely coronary remodelling.

The increase in lumen area would contribute to maintain a constant flow velocity in large epicardial arteries and as a consequence a normal endothelial function with a normal shear stress. This would result in a reduced release of endothelium-derived relaxing factor which is known to be a potent vasodilator, inhibits proliferation of vascular smooth muscle cells, endothelial movement and extracellular matrix production.14

In an experimental model in rats, coronary hypertension (banding of ascending aorta) without hypertrophy (right ventricle) remodelling was expressed in arterial microvessels larger than 30 μm but not in small microvesels (30 μm). Medial thickening by proliferation of smooth muscle cells and perivascular fibrosis were observed.15

On the other hand, in myocardial hypertrophy without coronary hypertension (pulmonary artery banding) no vascular hypertrophy was observed, but deposition of collagen in perivascular tissues of small microvesels (<60 μm in lumen diameter).15 Cardiac renin-angiotensin-aldosterone system, endothelial growth factor, platelet derived growth factors, atrial natriuretic peptide, and endothelin among other susbstances may be involved in this response.16 Increased wall stress owing to pressure overload may stimulate perivascular fibroblasts proliferation and extracellular matrix proteins by these cells.

When coronary hypertension is combined with hypertrophy, as is often the case in systemic arterial hypertension, the two remodelling processes described are superimposed.17 Medial hypertrophy and perivascular collagen deposition have been observed in small and larger microvessels in a study in humans by biopsy samples18 and in autopsies of hypertensive patients.19

Experimental data show that after relief of pressure overload there is a regression of medial hypertrophy and perivascular collagen, first at larger arterial microvessels and then in small microvessels17 but perivascular collagen deposition may remain.20 Capillary density (capillary number by unit area) is decreased in hypertrophic muscle and may also regress after treatment.20

Either due to coronary atherosclerosis or to a decreased coronary reserve, clinical manifestations of CHD (angina, myocardial infarction) are frequent in hypertensive patients. Resting electrocardiogram show alterations of repolarisation suggestive of ischaemia and exercise tests may have a false-positive response. Ischaemia may also contribute to produce subendocardial fibrosis which in turn contribute to diastolic as well as to systolic dysfunction.

It has been suggested that acute coronary syndromes might be favoured by an increased flow velocity and shear stress which could contribute to plaque disruption. It has been shown in hypertensive patients with normal coronary arteries that flow velocity is increased which is only partially reversed by isosorbide.21

In hypertensives with left ventricular hypertrophy the risk of reinfarction, overall mortality and mortality due to CHD are significantly increased.22

It is important to emphasise that treatment of hypertension reduces significantly the number of fatal and non-fatal cardiovascular events in patients with CHD.23,24

General principles for the treatment of hypertension fully apply to patients with hypertension and CHD. Recent data from the Hypertension Optimal Treatment (HOT) Trial in a cohort of 19000 patients, show no evidence of increased mortality when diastolic blood pressure fell below 85 mm Hg, contradicting former data of an increased mortality when treated diastolic blood pressure fell below that figure (J curve).25 It is advisable to avoid sudden decreases in blood pressure values and tachycardia when angina pectoris is present. Vasodilator agents may cause reflex stimulation of baroreceptors and tachycardia and increased contractility resulting in increased myocardial oxygen demand and thus aggravating angina. On that respect, hydralazine or short-acting calcium antagonists should be avoided.

Global evaluation of the patient is mandatory. It is important to evaluate the extension of organic damage, the presence of diabetes and other risk factors, and the presence of aggravating factors such as thyrotoxicosis and anaemia, etc, and obviously the severity and extension of coronary disease. Non-pharmacologic and pharmacologic treatment must be linked to reduce overall cardiovascular risk.

Furthermore stabilisation of atherosclerotic plaque is of extreme importance. Antithrombotic agents, as well as statins when necessary, are important on these grounds. All other therapeutic considerations to treat CHD should be considered including revascularisation procedures.26

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Escobar, E. Hypertension and coronary heart disease. J Hum Hypertens 16, S61–S63 (2002). https://doi.org/10.1038/sj.jhh.1001345

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Keywords

  • hypertension
  • hypertrophy
  • coronary heart disease

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