Case history A 72-year-old woman sees her general practitioner because of an Escherichia coli urinary infection. Her blood pressure is 196/86 mmHg. She had had a small stroke two years previously, which was managed at home, and from which she made a complete recovery. At that time, her blood pressure was recorded as 160/80 mmHg. She looks after her husband (who has mild dementia) and enjoys life, particularly visits from her grandchildren. She smokes ten cigarettes/day, does not drink any alcohol and takes no drugs. The remainder of the examination is unremarkable. Serum creatinine is normal, total cholesterol is 5.6 mmol/L and HDL is 1.2 mmol/L. The urinary tract infection resolves with a short course of amoxicillin. This patient’s blood pressure on two further occasions is 176/84 and 186/82 mmHg, respectively. An ECG is normal. She is resistant to advice to stop smoking (on the grounds that she has been doing it for 55 years and any harm has been done already) and the suggestion of drug treatment (on the grounds that she feels fine and is ‘too old for that sort of thing’). Questions Decide whether each of the following statements is true or false. (a) This patient’s systolic hypertension is a reflection of a ‘stiff’ circulation, and drug treatment will not improve her prognosis. (b) Drug treatment of the hypertension should not be contemplated unless she stops smoking first. (c) If she agrees to take drugs such as thiazides for her hypertension, she will be at greater risk of adverse effects than a younger woman. (d) Attempts to discourage her from smoking are futile. (e) An α 1-blocker would be a sensible first choice of drug, as it will improve her serum lipid levels. (f) Aspirin treatment should be considered. Answer (a) False (b) False (c) True (d) False (e) False (f) True. Comment Treating elderly patients with systolic hypertension reduces their excess risk of stroke and myocardial infarction. The absolute benefit of treatment is greatest in elderly people (in whom events are common). Treatment is particularly desirable as this patient made a good recovery from a stroke. She was strongly discouraged from smoking (by explaining that this would almost immediately reduce the risk of a further vascular event), but she was unable to stop. Continued smoking puts her at increased risk of stroke and she agreed to take bendroflumethiazide 2.5 mg daily with the goal of staying healthy so that she could continue to look after her husbandand enjoy life. She tolerated this well and her blood pressure fell to around 165/80 mmHg. The addition of a long-acting ACE inhibitor (trandolapril, 0.5 mg in the morning) led to a further reduction in blood pressure to around 150/80 mmHg. α 1-Antagonists can cause postural hypotension, which is particularly undesirable in the elderly. FURTHER READING OTHER ANTIHYPERTENSIVE DRUGS 195 Dahlof B, Sever PS, Poulter NR et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; 366: 895–906. Furberg CD, Wright JT, Davis BR et al. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone – The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Journal of the American Medical Association 2000; 283: 1967–75. Furberg CD, Wright JT, Davis BR et al. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic – The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Journal of the American Medical Association 2002; 288: 2981–97. Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. New England Journal of Medicine 1996; 334: 1649–54. Palmer BF. Current concepts: Renal dysfunction complicating the treatment of hypertension. New England Journal of Medicine 2002; 347: 1256–61. Setaro JF, Black HR. Refractory hypertension. New England Journal of Medicine 1992; 327: 543–7. Sibai BM. Treatment of hypertension in pregnant women. New England Journal of Medicine 1996; 335: 257–65. Staessen JA, Li Y, Richart T. Oral renin inhibitors. Lancet 2006; 368: 1449–56. Swales JD (ed.). Textbookof hypertension. Oxford: Blackwell Science, 1994. van Zwieten PA. Central imidazoline (I1) receptors as targets of centrally acting antihypertensives: moxonidine and rilmenidine. Journal of Hypertension 1997; 15: 117–25.
● Pathophysiology 196 ● Management of stable angina 196 PATHOPHYSIOLOGY CHAPTER 29 ISCHAEMIC HEART DISEASE Ischaemic heart disease is nearly always caused by atheroma (Chapter 27) in one or more of the coronary arteries. Such disease is very common in western societies and is often asymptomatic. When the obstruction caused by an uncomplicated atheromatous plaque exceeds a critical value, myocardial oxygen demand during exercise exceeds the ability of the stenosed vessel to supply oxygenated blood, resulting in chest pain brought on predictably by exertion and relieved within a few minutes on resting (‘angina pectoris’). Drugs that alter haemodynamics can reduce angina. Most patients with angina pectoris experience attacks of pain in a constant stable pattern, but in some patients attacks occur at rest, or they may occur with increasing frequency and severity on less and less exertion (‘unstable angina’). Unstable angina may be a prelude to myocardial infarction, which can also occur unheralded. Both unstable angina and myocardial infarction occur as a result of fissuring of an atheromatous plaque in a coronary artery. Platelets adhere to the underlying subendothelium and white thrombus, consisting of platelet/fibrinogen/fibrin aggregates, extends into the lumen of the artery. Myocardial infarction results when thrombus occludes the coronary vessel. In addition to mechanical obstruction caused by atheroma, with or without adherent thrombus, spasm of smooth muscle in the vascular media can contribute to ischaemia. The importance of such vascular spasm varies both among different patients and at different times in the same patient, and its contribution is often difficult to define clinically. The mechanism of spasm also probably varies and has been difficult to establish. A variety of vasoconstrictive mediators released from formed elements of blood (e.g. platelets or white cells) or from nerve terminals may contribute to coronary spasm. Its importance or otherwise in the majority of patients with acute coronary syndromes is a matter of considerable debate. Treatment of patients with ischaemic heart disease is directed at the three pathophysiological elements identified above, namely atheroma, haemodynamics and thrombosis. New onset of chest pain at rest or crescendo symptoms should raise suspicion of unstable angina or myocardial infarction, ● Management of unstable coronary disease 198 ● Drugs used in ischaemic heart disease 200 and emergency referral to a hospital with coronary care unit. The general management of stable angina is illustrated in Figure 29.1 and detailed further below. MANAGEMENT OF STABLE ANGINA MODIFIABLE RISK FACTORS Modifiable risk factors include smoking, hypertension, hypercholesterolaemia, diabetes mellitus, obesity and lack of exercise. The object of defining these factors is to improve them in individual patients, thereby preventing progression (and hopefully causing regression) of coronary atheroma. This is discussed in Chapters 27, 28 and 37. PAIN RELIEF An attack of angina is relieved by glyceryl trinitrate (GTN), which is given by sublingual administration. However, in patients with chronic stable angina, pain usually resolves within a few minutes of stopping exercise even without treatment, so prophylaxis is usually more important than relief of an attack. In patients hospitalized with acute coronary syndrome, GTN is often administered by intravenous infusion; its short half-life allows rapid titration, thus permitting effective pain relief whilst promptly averting any adverse haemodynamic consequences (in particular, hypotension). PROPHYLAXIS Figure 29.2 outlines the drug treatment of stable angina. Antithrombotic therapy with aspirin reduces the incidence of myocardial infarction; its use and mechanism of action as an antiplatelet agent are discussed further in Chapter 30. Prophylaxis is also directed at reducing the frequency of attacks of angina. In this context, GTN is best used for ‘acute’ prophylaxis. A dose is taken immediately before undertaking activity that usually brings on pain (e.g. climbing a hill), in