Brought to you by Diabetes & Primary Care, the three mini-case studies presented here take you through the considerations of managing complex cases of hypertension in type 2 diabetes. This module should be worked through once you have completed Managing hypertension in diabetes – the basics. Each scenario provides a different set of circumstances that you could meet in your everyday practice. By actively engaging with them, you will feel more confident and empowered to manage effectively such problems in the future
- NICE (2019) Hypertension in adults: diagnosis and management (NG136). www.nice.org.uk/guidance/ng136
- Williams B, MacDonald TM, Morant S et al; British Hypertension Society’s PATHWAY Studies Group (2015) Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised double-blind, crossover trial. Lancet 386: 2059–68
- de Boer IH, Bangalore S, Benetos A et al (2017) Diabetes and Hypertension: A position statement by the American Diabetes Association. Diabetes Care 40: 1273–84
- Fleg JL, Evans GW, Margolis KL et al (2016) Orthostatic hypotension in the ACCORD blood pressure trial: prevalence, incidence and prognostic significance. Hypertension 68: 888–95
- Arguedas JA, Leiva V, Wright JM (2013) Blood pressure targets for hypertension in people with diabetes mellitus. Cochrane Database Syst Rev 10: CD008277
- Zhao P, Xu P, Wan C, Wang Z (2011) Evening versus morning dosing regimen drug therapy for hypertension. Cochrane Database Syst Rev 10: CD004184
- Hermida RC, Ayala DE, Mojón A, Fernández JR (2011) Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care 34: 1270–6
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Winston is a 67-year-old man of Afro-Caribbean ethnicity with type 2 diabetes for 15 years. He has always struggled with control of hypertension and his blood pressure (BP) is currently around 155/78 mmHg (confirmed with home BP monitoring) despite triple therapy with lisinopril 20 mg once daily, indapamide 2.5 mg once daily and amlodipine 10 mg once daily. His eGFR is 65 mL/min/1.73 m2 and ACR is 2.2 mg/mmol.
What BP target should we be aiming for in Winston? Discuss what you might do in this next consultation?
This response will be awarded full points automatically, but it can be reviewed and adjusted after submission.
A reasonable target BP for Winston would be 140/90 mmHg (1). Ascertain that Winston has recorded his BP readings in the correct fashion and check that he has been taking all his antihypertensive medications regularly and appropriately. It is worth reviewing his glycaemic control and other investigations to see these are up to date, and that due consideration has been given to controlling other cardiovascular risk factors. Reinforce lifestyle measures that can benefit hypertension.
What further options do you have to manage Winston’s hypertension?
Winston has, by definition, resistant hypertension (BP not controlled despite triple therapy).
There is evidence that aldosterone receptor antagonists are the most effective add-on drug for resistant hypertension (2), and both NICE and the American Diabetes Association recommend their use at this stage (1,3).
Usually, low-dose spironolactone is chosen, but should gynaecomastia prove problematic with spironolactone, then eplerenone may be tried. Care should be taken to check for hyperkalaemia – both before initiation (avoid starting if serum potassium levels are ≥4.5 mmol/L (1)) and within a few weeks of starting (along with repeat eGFR). The risk of hyperkalaemia is raised if ACE inhibitors/ARBs are also being prescribed, as here, and if there is pre-existing renal failure. To some extent the hyperkalaemia can be countered by use of potassium-losing diuretics. Remember that aldosterone antagonists do have a beneficial effect in heart failure.
If Winston had problems with hyperkalaemia or renal function following introduction of spironolactone, what further options might you consider for BP control?
You might reasonably try an alpha-blocker (e.g. doxazosin) or a cardioselective beta-blocker (e.g. bisoprolol) (1).
What side effects might you warn patients about with use of these two classes of medication, and in what situations might their use be favoured?
Warn patients about the symptoms of postural hypotension when commencing an alpha-blocker. They may be selected preferentially in men suffering urinary flow problems secondary to prostatic hyperplasia.
A potential disadvantage of beta-blockers is blunting of the adrenergic response (and hence warning signs) to hypoglycaemia induced by sulfonylureas or insulin. There may be worsening of symptoms in patients with obstructive airway disease (avoid in asthma) and peripheral vascular disease. However, beta-blockers do have a protective role in ischaemic heart disease, post-myocardial infarction and heart failure, and are likely to be used in these situations.
If, however, BP remains above target with optimal tolerated doses of four drugs, then specialist advice will be required (1,3).
Lily is a 79-year-old lady with type 2 diabetes for 12 years and appropriate glycaemic control for her age (62 mmol/mol on linagliptin 5 mg once daily and Lantus 16 units at night). She takes triple antihypertensive therapy, and her current BP is 155/70 mmHg. Her ramipril dose was halted at 5 mg once daily because of concerns about renal function (current eGFR averages around 30 mL/min/1.73 m2 and ACR 1.9 mg/mol), and lercanidipine dose is limited to 10 mg once daily because of bilateral ankle oedema. She also takes bendroflumethiazide 2.5 mg once daily. Lily lives alone and suffers from osteoarthritis, using a stick to help mobilise.
What would be your concerns over intensifying Lily’s antihypertensive therapy?
Postural hypotension is a major concern in treating hypertension in the elderly. This risk may be increased in Lily’s case by volume depletion, secondary to use of a diuretic, and possibly by diabetic autonomic neuropathy (4). Lily is already more susceptible to a fall because of her arthritis and need to use a stick when mobilising. It would be worth checking her seated and standing BP.
Introduction of further antihypertensive therapy may trigger postural hypotension in addition to side-effects specific to that medication as well as compounding the problems of polypharmacy.
It seems that the Lily’s ramipril and lercanidipine doses are already at their upper tolerated limits. By the time eGFR has fallen to 30 mL/min/1.73 m2, then loop diuretics (e.g. furosemide, bumetanide) become more effective than thiazide-like diuretics. This switch might be considered as a means of reducing ankle oedema, although the risk of volume depletion and electrolyte disturbance remains (so a follow-up test of renal function and electrolytes would be indicated in this situation). A loop diuretic would lead to increased urgency and frequency of micturition which, combined with her poor mobility, is even more likely to result in falls. Spironolactone therapy runs the risk of hyperkalaemia and worsening of renal function. Dizziness may result from treatment with alpha-blockers (postural hypotension) and beta-blockers (bradycardia).
What would you consider to be a reasonable BP treatment target for Lily?
NICE guidelines would suggest an ideal BP target of <150/90 mmHg for an individual with type 2 diabetes aged ≥80 years, but emphasises the need for individualisation of therapy (1). Lily has significant comorbidities and would be vulnerable to problems associated with intensification of antihypertensive therapy, so a relaxation of this target would be appropriate in her situation.
Lily’s systolic and diastolic BP decreased by approximately 9 mmHg and 3 mmHg respectively when comparing standing to sitting. When a discrepancy in readings occurs, NICE recommends using standing readings to set the BP target (1).
After discussion with Lily over the pros and cons of further treatment, it was agreed to continue with her current antihypertensive therapy. The opportunity was taken to reinforce lifestyle measures, including the importance of avoiding added salt to food and maintaining a high-fibre diet.
Which is the more important BP target for Lily – systolic or diastolic?
It is generally accepted that systolic BP is a more powerful prognostic indicator across age ranges. Whilst diastolic BP is an important predictor of morbidity in younger people, it becomes less important with age (5). Indeed, many elderly people like Lily will have isolated systolic hypertension, and the dilemma then becomes what is a safe systolic BP to aim for if diastolic BP is low (especially if <60 mmHg).
Whilst the thrust of antihypertensive treatment for Lily is directed toward lowering her systolic BP, we need to aware of her relatively low diastolic BP and mindful of the risk of postural hypotension.
Mark is 47 years old and presented at his GP surgery with persistent genital thrush. A (non-fasting) capillary glucose reading of 14.3 mmol/L was recorded. He is obese (BMI 36.4 kg/m2) and, with a family history of type 2 diabetes, it seems very likely he himself has type 2 diabetes. Mark has no osmotic symptoms.
Further investigations were organised and the diagnosis of diabetes confirmed. At a follow-up appointment, a BP of 194/126 mmHg is recorded (on repeat measurement).
What findings might prompt you to refer Mark immediately to hospital?
NICE recommends immediate referral for specialist assessment in people with a clinic BP >180/120 mmHg if there are signs of retinal haemorrhage or papilloedema (accelerated or malignant hypertension), or if there is associated chest pain, signs of heart failure, evidence of acute kidney injury or new onset confusion (1). Headache, palpitations, abdominal pain and excessive sweating may also indicate serious complications or conditions associated with hypertension (e.g. phaeochromocytoma).
How would you respond to Mark’s raised BP?
Investigations, notably for target organ damage, should be undertaken as a matter of urgency in this case of severe (stage 3) hypertension (clinic BP ≥180/120 mmHg) (1). These should include:
- Examination of the fundi, looking for retinal haemorrhages and papilloedema
- Cardiac auscultation
- Examination for signs of heart failure: auscultation of lung bases, peripheral oedema
- U+E, eGFR, LFT, lipid profile
- Dipstick urine for haematuria, proteinuria
- Urine sample for ACR
Consider starting Mark on antihypertensive treatment immediately, especially if there is evidence of target organ damage (without waiting for follow-up BP measurement, ABPM or HBPM). If target organ damage is not identified and antihypertensive medication is not immediately commenced, then a repeat clinic BP in 7 days should be arranged (1).
Is there a best time to take antihypertensive medication?
There is evidence that BP is slightly better controlled when antihypertensives are taken in the evening (rather than the morning) (6), and taking at least one antihypertensive at this time can significantly reduce cardiovascular events in individuals with type 2 diabetes (7).
So, can you summarise a pathway to BP treatment in individuals with type 2 diabetes?
Suggested approach to treating hypertension in patients with diabetes (1,3).
First line: ACE inhibitor (e.g. ramipril) or ARB (e.g. losartan)
Second line: Dihydropyridine CCB (e.g. amlodipine)
or thiazide-like diuretic (e.g. indapamide)
Third line: Add second-line agent not already used
Triple therapy of: ACEi/ARB + DHPCCB + thiazide like diuretic
Fourth line: Aldosterone receptor antagonist (e.g. spironolactone)
or if potassium >4.5 mmol/L, beta-blocker (e.g. bisoprolol)
or alpha-blocker (e.g. doxazosin)
Some concluding notes on treating hypertension in type 2 diabetes are shown in the following section.
Hypertension occurs more frequently in people with diabetes than in those without. It is a common comorbidity in type 2 diabetes that is associated with an increased risk of macrovascular and microvascular complications. Treating hypertension in diabetes reduces the risk of stroke, cardiovascular disease, nephropathy and retinopathy.
Most evidence-based guidelines advocate a target BP of 135–140/85–90 mmHg in diabetes (see “Making sense of blood pressure readings in those with diabetes”). However, this target should be individualised according to age and comorbidity. A lower value of 130/80 mmHg may be appropriate in people with nephropathy or previous stroke (see previous module on “Managing hypertension in diabetes – the basics”). Higher BP targets may be appropriate in the elderly.
The starting point for treating hypertension is lifestyle adjustment. Losing weight, exercising regularly, avoiding excess alcohol consumption, dietary adjustment and reducing salt intake are important.
Satisfactory BP control is more important than choice of antihypertensive agent. Usually a combination of antihypertensive treatments will be necessary to achieve the desired BP target. ACE inhibitors and ARBs are regarded as first-line antihypertensives in diabetes. They offer renoprotection to people with diabetic nephropathy and cardiovascular benefits. Dihydropyridine CCBs and thiazide-like diuretics are second- and third-line agents for hypertension in diabetes. Spironolactone can be helpful in resistant hypertension.
Age, comorbidities, current medication, biochemistry and social factors will influence the choice of antihypertensive agent.