When a patient sitting in the clinic does not meet guideline criteria for hypertension and dyslipidaemia, as often happens, then it is time to call on experience and clinical judgement. For example, the Systematic Coronary Risk Evaluation (SCORE) charts used to estimate cardiovascular events over 10 years are less predictive for younger patients and don’t take into account family history, socioeconomic status, sedentary lifestyle, central obesity or low high-density lipoprotein (HDL), so patients may be falsely reassured by their SCORE result.
Meanwhile, using relative risk charts or cardiac age estimates may assist but trying to ‘scare’ patients into lifestyle modification by telling a hypertensive 40-year-old male smoker that he has a cardiac risk age of 65 is to use ‘false facts’. We need to be honest in explaining that we do not know an individual’s future CV risk but we have epidemiology evidence to guide us in our decision-making.
Therefore, we combine trial data and our clinical judgement to extrapolate to the patient sitting in front of us. The treatment is therefore patient-centric, involving the patient’s preferences and beliefs, including, potentially, their refusal to take any treatment. If the patient feels involved in the decision-making process they are more likely to be compliant, which improves patient outcomes.
This is a conversation as to how to explain the manner by which antihypertensives reduce risk of stroke:
<em>‘High blood pressure doesn’t cause a stroke by bursting an artery in your brain (this is what many worry about). However, over years, the tiny arteries in your brain become thicker due to high pressure to protect themselves. Unfortunately, this protective thickening causes the channel to narrow and if left untreated, in 20 years the arteries become so narrow that the blood clots and causes a mini-stroke. These mini-strokes may present with balance, speech or memory issues or you may get a large stroke, with weakness of one side. </em>
<em>‘However, by lowering your BP now, these small arteries in your brain won’t thicken and this will reduce your stroke risk in years to come, as well as reduce your risk of a heart attack or kidney failure and possibly even dementia.’</em>
Some side-effects of antihypertensives include, but are not limited to: Amlodipine causes oedema, ACEi cause cough and rash, ARB causes rash and headaches, diuretics cause gout, urinary frequency and postural symptoms in the elderly, alpha blockers causes postural hypotension and finally, beta blockers cause fatigue and cold peripheries but are rarely used for hypertension, unless there is some other indication, such as angina.
<h3 class=”subheadMIstyles”>Dyslipidaemia</h3>
Assuming the patient’s BP is now controlled, you need to address his lipid profile so you arrange fasting cholesterol (>12 hours, so no food after 8pm) and his total cholesterol is now 6.0, LDL 4.1, HDL 1.2mmol/L. The earlier non-fasting sample had given a falsely ‘acceptable’ LDL level of 3.8, as non-fasting samples underestimate LDL concentration due to chylomicrons, which affect the Friedewald equation: LDL = tChol — HDL — trigs/5 (assuming trigs <4.5).
Cardiac risks are cumulatively bad — in other words, each risk makes the other risk more of a concern. As the patient has confirmed Grade 1 hypertension, his cholesterol needs to be treated. The same issues arise, namely, he is reluctant to take statins as he heard they cause memory loss. You explain there is no evidence of this but the rumour began as statins are often started in older patients at a time when their memory is failing. This is only a temporal relationship rather than a causative relationship and there is even some evidence of cognition preservation on statins.
This is a suggestion as to how to explain how statins reduce heart attacks.
<em>‘Statins do more than lower your cholesterol level in your blood. Your coronary arteries dilate when you exercise, as your heart needs more blood flow. They dilate by releasing nitric oxide from the lining of the artery in response to increased flow. By dilating, there is less stress on the wall of the artery. However, with cholesterol in the walls of the coronaries, it reduces nitric oxide release, so the artery doesn’t dilate. The blood then flows through a narrower channel, causing stress on the lining of the wall, which can disrupt the lining, allowing more cholesterol to be deposited and a vicious circle starts. </em>
<em>‘Finally, an asymptomatic 30 per cent cholesterol blockage may rupture due to the stress of the fast blood. Blood is then exposed to the cholesterol and a clot will block the remaining 70 per cent of the artery, causing a heart attack. The heart attack may result in sudden death if there is a rhythm disturbance; all from a 30 per cent narrowing. What statins do is, they stabilise the 30 per cent blockage by making it firm, so it won’t rupture. In summary, statins can turn a ‘hot, soft, vulnerable, dangerous plaque’ into a ‘cold, hard, stable, safe plaque’. We use the LDL level as a marker of this process.’</em>
To explain the concept of cholesterol plaque, I use an analogy of teenage acne or a spot with a thin cover, ‘<em>which may burst and yellow pus comes out. This yellow stuff is what cholesterol is like in the walls of the artery. But if the spot is treated, it will heal and become a hard lump that won’t burst, ie, it will be rendered a hard, cold, safe lump</em>’. This is not a nice image, but effective, as we all remember spots in our youth.
Therefore, now your 56-year-old patient is on an antihypertensive and a statin and his compliance has improved as his understanding of the indications is informed. You hope from the clinical trial data that when he turns 76, you will have prevented potential adverse cardiovascular events to promote a healthy retirement.
It would be remiss of me not to mention new treatments available this year for treating familial dyslipidaemia or those with above-target LDL levels despite statin therapy, or statin-intolerant patients, namely the PCSK9 inhibitors. These are injected subcutaneously fortnightly.
Indications are primary hyperlipidaemia for heterozygous familial hypercholesterolaemia or clinical atherosclerotic CVD who require additional LDL-C lowering, despite diet and maximally-tolerated statins or for homozygous familial hypercholesterolaemia.
These are monoclonal antibodies that inactivate PCSK9, which results in decreased degradation of LDL receptors and increased recirculation of the LDL receptors on to the surface of hepatocytes. This dual effect results in marked reduction of LDL levels between 40-to-60 per cent.
The long-anticipated cardiovascular outcome trial of 27,000 patients randomised to evolocumab (Repatha) vs placebo in the FOURIER trial was due to be presented at the American College of Cardiology (ACC) meeting in Washington DC on 17 March by Amgen, just as this article went to press.
However, the company has already announced that the drug met its primary composite end-point of reduction in cardiovascular death, non-fatal MI, non-fatal stroke, hospitalisation for unstable angina or coronary revascularisation.
These results and the results of the other PCSK9 inhibitor, alirocumab (Praluent) in the Odyssey Outcomes study by Sanofi of 18,600 patients next year will herald a new era of achieving optimal LDL-lowering and better outcomes for those whose future currently includes a cardiovascular event.
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<h3 class=”bodytextMIstyles”>Case study</h3>
An otherwise healthy 56-year-old man attends a health check at work. He is hypertensive BP 170/90mmHg, heart rate 76 bpm. He was referred to his GP. He is asymptomatic with normal ECG, with no diabetes or family history. Non-fasting cholesterol 5.8, LDL 3.8 and HDL 1.3 with triglycerides 2.2mmol/L. He was obese, BMI 30kg/m<sup>2</sup>, weight 93kg (14 st 9 lb) and height 176cm (5’ 9”). He smoked 10/day until age 35.
<strong>Options:</strong>
<p class=”listnumberedallotherlinesMIstyles”>Refer to emergency department (ED), as concerned about stroke risk. Advantages are that he may be admitted for all necessary tests and commence treatment if appropriate. (This may be the most comprehensive course of action but ED waiting times are an issue.)
<p class=”listnumberedallotherlinesMIstyles”>Refer to specialist physician (general, cardiology, renal, endocrine but the public waiting list is a few months; private is prompt but costly.)
<p class=”listnumberedallotherlinesMIstyles”>Commence Istin 5mg and atorvastatin 10mg and review in six weeks with check on BP and repeat fasting lipids.
<p class=”listnumberedallotherlinesMIstyles”>Commence Istin and advise diet and exercise and repeat lipids in six weeks.
<p class=”listnumberedallotherlinesMIstyles”>Start nothing, but advise diet and exercise and review in six weeks with fasting lipids and check BP after diet, salt restriction and exercise.
<p class=”listnumberedallotherlinesMIstyles”>Clarify diagnosis with home BP readings using an Omron Basic M2 BP monitor.
<p class=”listnumberedallotherlinesMIstyles”>Arrange 24-hour ABPM, through your own rooms or through pharmacy, cost approx €50-60.
Choice 7: a) The ABPM shows mean BP 140/86 (target <130/85mmHg) but some good readings 110/70mmHg with a normal nocturnal dip, so you reassure patient and advise as per option 5 above.
Choice 7: b) The ABPM shows mean BP 156/90mmHg with blunted nocturnal dip. There are adequate numbers of interpretable BP readings (>90%) and no stress or disturbed sleep: You have confirmed patient has Grade 1 hypertension. He also has other risks, being male, 56 years old with BMI 30kg/m2 and an ex-smoker with mild dyslipidaemia.
<strong>So how are you going to proceed?</strong> Options 1-4 are still applicable: Refer to ED, specialist, start Istin and statin or just an antihypertensive drug and trial of diet for dyslipidaemia. The choice of antihypertensive would be guided by a number of factors, but at his age, best to start with an ACEi but warn him about cough. If female, known asthma or sinusitis where cough may be an issue, you might commence ARB instead. If Grade 2 hypertension, you might commence combination therapy with ACEi/CCB or ARB/CCB eg Acerycal 5/5mg or Konverge 20/5mg. Often best to start low to reduce side-effects to improve initial compliance and then titrate.
<strong>But what if this patient is reluctant to take drugs?</strong> In this case, the question is, how strong is the evidence for BP treatment and how urgent is treatment? It is best to be honest and explain that there is no rush to treatment. Explain there is no immediate danger. Suggest repeat ABPM after trial of lifestyle change. Suggest a ‘trial of therapy’ so he doesn’t feel committed to a lifetime on drug treatment. Then when he sees the improved ABPM on treatment, he can make a more informed decision to remain on treatment for life.
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