Kumar 10th Edition Hypertension PDF

31 Hypertension Vikas Kapil Introduction Clinical approach to the patient with hypertension Measurement of blood pressure Phenotypes of hypertension Causes of raised blood pressure Secondary hypertension Thresholds and targets in hypertension 1133 1134 1134 1136 1137 1138 1138 CORE SKILLS AND KNOWLE...

31 Hypertension Vikas Kapil Introduction Clinical approach to the patient with hypertension Measurement of blood pressure Phenotypes of hypertension Causes of raised blood pressure Secondary hypertension Thresholds and targets in hypertension 1133 1134 1134 1136 1137 1138 1138 CORE SKILLS AND KNOWLEDGE Hypertensive target organ damage Treatment Lifestyle changes Drug treatment Future approaches Managing blood pressure in hospital 1138 1140 1140 1140 1142 1143 Key skills in hypertension include: individual’s overall cardiovascular risk Hypertension is a major cardiovascular risk factor affecting onethird of the adult population. It should be managed as part of a comprehensive cardiovascular risk reduction strategy, while also assessing for hypertensive end-organ damage and ruling out secondary causes. Treatment involves modifying lifestyle to improve diet and body weight, and making use of a range of antihypertensive medications. Most hypertension is managed in primary care. However, young patients with hypertension, or patients who have uncontrolled hypertension despite taking three or more antihypertensives, should be referred for expert evaluation. Doctors may subspecialize in the management of hypertension after completing training in clinical pharmacology, cardiology, renal medicine or another medical specialty. INTRODUCTION Raised blood pressure (BP) is the leading risk factor for death worldwide, outstripping tobacco smoking, poor sanitation and infectious diseases. It is a leading risk factor for atrial fibrillation, stroke, myocardial infarction and end-stage kidney disease. It is such a powerful predictor of these cardiovascular events that modern drug therapies are licensed for cardiovascular protection simply on evidence of sustained BP reduction. Hypertension refers to the persistent elevation of BP in the systemic arterial circulation. It is the most common chronic health condition for which patients receive medication from their primary care doctor and is associated with 1 in 10 of all primary care appointments. It affects one-third of adults and this number continues to rise in all populations. Annual drug costs related to hypertension are well in excess of £1 billion in the UK. Hypertension is diagnosed against threshold levels of BP from the evidence gathered from large multicentre, multinational studies. evidence of end-organ damage pertension, and becoming familiar with the main classes of drug used. Gaining experience in the practical management of hypertension is best done during primary care attachments: for instance, by observing patients undergoing annual blood pressure medication reviews with their general practitioner. Attending a specialist hypertension clinic in a secondary or tertiary care setting gives an interesting insight into secondary causes and more severe phenotypes of hypertension.␣ However, given the continuous relationship between BP and cardiovascular disease (Fig. 31.1) and renal morbidity, there is a trend towards basing treatment on even lower thresholds, and towards using total cardiovascular risk (see p. 751) to guide decisions on whether lowering BP is of benefit in individual patients. The majority of patients with hypertension are managed in primary care, with specialist hospital services usually reserved for evaluation of secondary causes, or for those patients with problematic BP phenotypes (see p. 1136) or medication intolerances. Despite the wide availability of diagnostics (i.e. BP monitors) and proven treatments (i.e. medications), reduction of BP in hypertensive patients to target levels is less than 50% in most populations and remains the focus of renewed efforts on an international, national and local scale. Hypertension is a disease of ageing. It is rare in children and adolescents, and a diagnosis in those under 30 years of age requires careful evaluation of possible underlying secondary causes (see p. 1136). Due to age-related stiffening in large arterial structure 1133 1134 Hypertension SBP and CHD SBP and stroke 8.00 8.00 4.00 4.00 Relative risk and 95% confidence intervals Relative risk and 95% confidence intervals 31 2.00 1.00 0.50 0.25 2.00 1.00 0.50 0.25 110 120 130 140 150 160 170 110 120 130 140 150 160 170 Usual SBP (mmHg) Usual SBP (mmHg) Fig. 31.1 The relationship between blood pressure and cardiovascular morbidity. CHD, coronary heart disease; SBP, systolic blood pressure. (Jackson et al. Lancet 2005; 365: 434-441.) (arteriosclerosis), BP tends to increase throughout middle and later life. Female sex hormones appear to protect against raised BP, as women have lower BP levels at all ages until menopause, when both prevalence of hypertension and achieved BP levels approximate to those of men. Hypertension is more common in certain ethnic groups (black African, African–Caribbean) and is also associated with urbanized and migrant populations, although an unequivocal explanation for these phenomena is not agreed.␣ CLINICAL APPROACH TO THE PATIENT WITH HYPERTENSION Hypertension is largely asymptomatic, though it is associated with increased prevalence of headaches, epistaxis and, less commonly, other neurological symptoms such as visual disturbance and dizziness. Furthermore, in the absence of a hypertensive emergency syndrome (see p. 1144), symptoms related to raised BP are not an indication for treatment. Indeed, antihypertensive therapy is more likely to be the cause of adverse symptoms, such as postural intolerance. History and examination should seek out identifiable causes of raised BP and asymptomatic organ damage. There are four key considerations in the clinical assessment of patients with hypertension (Fig. 31.2) that can be determined through history, examination and investigations: - History This should cover: drug use, tobacco smoking, exercise, stressors (work and personal) ␣ Examination and investigations These should include: Fig. 31.2) ␣ MEASUREMENT OF BLOOD PRESSURE Due to the non-continuous, pulsatile blood flow maintained by the cardiac cycle, BP is represented by two numbers: systolic (peak arterial pressure during cardiac contraction) and diastolic (lowest arterial pressure during cardiac relaxation). It is presented as systolic pressure/diastolic pressure in mmHg (millimetres of mercury). BP is dynamic and has patterns of variability over seconds (related to breathing, sympathetic activation), minutes (exertion), hours (wake– sleep, circadian hormonal patterns) and the longer term (seasonal). Therefore, the measurement of BP and its use to determine the treatment of hypertension are inherently imprecise and a single measure may not reliably represent the usual (real) BP and its contribution to overall cardiovascular risk. As with any biological variable, the true usual BP is better approximated with multiple measurements at each assessment, and sometimes over several different assessment episodes, before decisions are made regarding changes in treatment. BP can be measured in several different locations on the body, though readings are traditionally taken in the non-dominant arm. Initially, the BP may be checked in both arms; if there is a significant difference (usually considered to be >10 mmHg), then the arm with the higher BP is used for subsequent measurements. It is important to measure BP in the correct manner. Methodological variation can falsely and hugely over- or underestimate BP. Measurement of blood pressure History duration of hypertension symptoms (headaches, vision, epistaxis – usually asymptomatic) co-morbidities (diabetes, CKD, CAD, stroke, gout) family history, particularly young hypertension and cardio-renal events hypertensive disorders of pregnancy, active attempt to become pregnant Secondary causes - see Box 31.2 1135 Thresholds (mmHg) Under 80 years: >140 or >90 (office) or >135 or >85 (ambulatory or home) Over 80 years: >160 or >90 (office) or >150 or >85 (ambulatory or home) Target (mmHg) In UK, 80% arm circumference Cuff at heart height Arm supported Box 31.1 Phenotypes of hypertension and corresponding BP measurements Phenotype/ method Office BP Out-of-office BP Cardiovascular risk Normotension Normal Normal Lowest White coat hypertension High Normal Intermediate Masked hypertension Normal High Intermediate Hypertension High High Highest Ambulatory measurement Legs uncrossed Back supported Uninterrupted rest for 5 min Fig. 31.3 Record at least two readings at each sitting The correct way to measure blood pressure. AF, atrial fibrillation. Issues with this approach include: time) decision-making (expense, time) care professionals is approximately 5/5 mmHg higher than at home, though there is inter-individual variation in the magnitude predictive of cardiovascular events, as patients do not live in healthcare settings. Although office BP is no longer recommended as the sole measure for diagnosis in many guidelines, it is still advocated for on-going monitoring and medication titration, as no cardiovascular outcome trials have used out-of-office readings to adjust treatment.␣ Home measurement This is measurement of BP at home by the patients themselves, of-office’ BP measurement and is closely approximated to daytime ambulatory BP. It is particularly useful for: making Current recommendations suggest that BP is measured on two or more occasions in sequence, in the morning prior to medicines and again in the evening for 4–7 days. The initial day’s readings are discarded and the rest of the values are averaged to calculate home BP. This BP is highly predictive of cardiovascular events and tends to be approximately 5/5 mmHg lower than that measured in the clinic. Issues with this approach include: patient-reported averages, rather than independent evaluations).␣ Ambulatory BP monitors are portable, oscillometric devices that measure BP discontinuously throughout a 24-hour period, most commonly every 20–30 minutes during waking hours and every 30–60 minutes during sleep. The large number of readings that this provides gives an accurate estimate of true BP. The 24-hour mean of the sequence of daytime and nocturnal BP measurements is more predictive of cardiovascular events than both home and office BP measurements. Ambulatory BP monitoring is now recommended in the UK instead of office BP for diagnosis, and is recommended as a complementary strategy to office BP in most other high-income health economies. Similar to home BP, ambulatory BP allows in a single measurement: Daytime ambulatory BP is 5–10/5 mmHg lower than office BP in the same patient. Issues with this approach include dislike of repeated BP measurement, especially at night.␣ PHENOTYPES OF HYPERTENSION The measurement techniques described can describe different phenotypes of hypertension (Box 31.1). Although both white coat hypertension and masked hypertension represent intermediate cardiovascular risk phenotypes, masked hypertension is treated using out-of-office values to guide treatment, while antihypertensives are not recommended for use in white coat hypertension, despite elevated cardiovascular risk, due to a current lack of evidence. There are other common phenotypes of hypertension: Isolated systolic hypertension Due to age-related arterial stiffening, systolic BP continues to rise in patients above 50 years of age, with a corresponding reduction in diastolic BP. This widening pulse pressure (the difference between systolic and diastolic BP, usually 1% per year, using validated cardiovascular risk equations), or evidence of organ injury due to hypertension (hypertensive target organ damage). Drug therapy is advocated, however, if BP fails to normalize after a 3–12-month period of besttolerated lifestyle changes. For the most part, then, the target has been an office BP of less than 140/90 mmHg, with stricter targets for patients with diabetes and proteinuric chronic renal disease (105 Isolated systolic hypertension >140 135 90%), which means that if criteria are positive, true left ventricular hypertrophy is likely to be present. ECGs are recommended in all hypertensive patients, as they are widely available and cheap, and do not require much in the way of additional training to interpret, especially as modern ECG machines have in-built reporting algorithms. However, cardiac imaging, using transthoracic echocardiography and cardiac MRI, is more sensitive and specific than ECG (when compared to autopsy data), though access, cost and need for additional trained staff to conduct and report these tests limit their wide utility and acceptance in all hypertensive patients. These cardiac imaging modalities can estimate the actual mass of the left ventricle; this is indexed to height and weight, and has sex-specific normal values.␣ Kidney Kidney disease is both a cause and a consequence of hypertension. Early hypertensive kidney damage is most easily detectable through an increase in microalbuminuria on urine test strips or as an increased laboratory albumin : creatinine ratio. Estimates of glomerular filtration rate (GFR), based on serum creatinine and demographic criteria, are also obtained, especially as several antihypertensive medications are potentially nephrotoxic. However, there is usually an initial reduction in GFR associated with chronic BP-lowering from any cause, and this usually reflects intra-renal haemodynamic changes rather than intrinsic renal damage; it is therefore common practice to allow GFR to reduce by up to 10% on initiation of antihypertensive therapy. More regular follow-up is mandated to ensure that this does not indicate progressive renal decline.␣ TREATMENT Meta-analyses of large-scale RCTs have shown that a 10/5 mmHg reduction in BP is associated with a 15% reduction in all-cause mortality, 35% reduction in stroke, 40% reduction in heart failure and 20% reduction in myocardial infarction. Hypertension is treated to reduce these major cardiovascular and renal events. For this reason, treatment of hypertension without managing other modifiable cardiovascular risk factors (raised cholesterol, diabetes mellitus, tobacco smoking, obesity) is suboptimal. Cardiovascular risk scores, such as QRISK2®, are useful for integrating all of these risk factors, to judge when there is benefit in treating hypertensive patients. Ten-year risk estimates are less useful than lifetime risk estimates in young patients, given the powerful role of age in all cardiovascular risk scores. Lifestyle changes These are recommended for all hypertensive patients, irrespective of grade or duration of disease. The BP reductions accompanying such lifestyle changes are complementary and similar in magnitude (compared to half-standard monotherapy) to those achieved by antihypertensive medications (Box 31.4). Bariatric surgery is indicated for those with hypertension and a body mass index (BMI) of more than 35 kg/m2, but it is not commonly performed without the additional co-morbidity of type 2 diabetes. Recent data confirm the profound BP-lowering effect of such surgery, which may be due to additional gut hormonal changes postoperatively, in addition to expected weight loss.␣ Drug treatment A single antihypertensive medication at standard dose reduces BP by about 9/5 mmHg in mild hypertension. Although patients with mild hypertension may achieve control with monotherapy, those with moderate or worse hypertension invariably require several drugs in combination. Greater effects are obtained by combining medications from different classes, targeting different mechanisms. Three antihypertensives at half-standard dose reduce BP by 20/11 mmHg. Most adverse effects with antihypertensives, in keeping with most pharmaceuticals, are type A adverse reactions (see p. 258) and are thus dose-dependent. Keeping doses to a minimum but combining different classes minimizes the chances of adverse effects and maximizes the likelihood of effectively lowering BP to target levels. As mentioned, adherence is increasingly recognized as a key barrier to achieving BP control. Although there are different validated measures to assess this, such as the Morisky-8 Medication Treatment 1141 A B C D E F Fig. 31.5 Hypertensive retinopathy. (A–B) Examples of mild hypertensive retinopathy. (A) Arteriovenous nicking (black arrows) and focal narrowing (white arrow). (B) Opacification (silver or copper wiring) of arteriolar wall (white arrows). (C–D) Examples of moderate hypertensive retinopathy. (C) A flame-shaped retinal haemorrhage (white arrow). (D) A cotton-wool spot (white arrow), retinal haemorrhages and microaneurysms (black arrows). (E–F) Severe hypertensive retinopathy. (E) Exudates and flame haemorrhages in grade 3 retinopathy. (F) Signs of malignant hypertension in grade 4 disease, with a swollen optic disc and macular exudate. (A–D From Schachat AP, Sadda SVR, Hinton DR et al. Ryan’s Retina, 6th edn. Elsevier Inc., 2018, Figs 52.1 and 52.2; E–F from Innes JA, Dover AR, Fairhurst K. Macleod’s Clinical Examination, 14th edn. Elsevier Ltd, 2018, Fig. 8.18CD.) 31 31 1142 Hypertension Box 31.4 Impact of lifestyle changes on BP Lifestyle change Expected mean BP reduction Regular cardiovascular exercise (30 min daily) 5 mmHg Weight reduction if overweight (body mass index >25 kg/m2) 1 mmHg/kg Increased intake of fruits and vegetables, reduced intake of saturated fat 10 mmHg Dietary salt reduction 180/110 mmHg) are associated with greater perioperative harm, such as myocardial injury, though there is no clear evidence that 31 31 1144 Hypertension reducing BP acutely in the preoperative period to controlled levels is beneficial. Patients with uncontrolled BP (evidence of chronic poor control of >160/100 mmHg in treated patients, or opportunistic measurements in pre-assessment in previously normotensive patients of >180/110 mmHg) are commonly referred back to their primary care doctor for adequate management of hypertension prior to elective procedures, though this is not a reason to delay necessary emergency surgical intervention. Although ACEIs and ARBs are often withheld arbitrarily for 24 hours preoperatively, it is usual to continue antihypertensive medications throughout the perioperative period unless there is documented hypotension or other related issues, such as withholding nephrotoxic antihypertensives if there is acute kidney injury.␣ Intraoperative Sympathetic activation during induction of anaesthesia can cause elevation of BP by 30 mmHg, with far larger responses in patients with untreated hypertension. Subsequently, with maintenance of anaesthesia, BP tends to fall due to the direct sympatholytic and vasodilating actions of anaesthetic drugs and loss of baroreflex regulation of BP. Patients with pre-existing uncontrolled hypertension are more likely to experience intraoperative BP lability (i.e. hypotension or hypertension), which is a risk factor for myocardial ischaemia and injury. Intraoperative hypertension is most commonly associated with inadequate analgesia or depth of anaesthesia, though it is prudent and recommended to exclude serious problems with airway, oxygen delivery and breathing first.␣ Postoperative Pain and (inadvertent) omission of antihypertensive medications are the most common reasons for postoperative hypertension. Once these factors have been corrected, there are no data to support the further active lowering of BP in the postoperative period without evidence of acute end-organ damage, though it is usual practice to try to keep BP below 180/110 mmHg, in part to reduce the risk of problems with postoperative haemostasis.␣ Blood pressure on the wards Patients with hypertension are often admitted to hospital for other medical reasons. Various factors can contribute to acute elevations of BP, such as antihypertensive medication omission, drug-induced hypertension (see earlier), anxiety, pain, bladder distension, recreational drug withdrawal and neurological injury. In the absence of a hypertensive emergency or other co-morbidity that requires acute BP management (e.g. to facilitate thrombolysis in acute stroke), uncontrolled BP does not require immediate management. However, as with most phenotypes, there is a threshold value that makes most healthcare professionals anxious about increased cerebral and cardiovascular risk, even in inpatients, and it is therefore common for BPs consistently above 180/110 mmHg to be treated, where there is no other clear precipitant. There is no role for short-acting drugs, such as sublingual glyceryl trinitrate (GTN) or nifedipine, and titration of standard chronic therapies with on-going monitoring is preferred.␣ Hypertensive emergencies Only a small subset of patients with significantly elevated BP (usually >180/120 mmHg) have signs or symptoms of acute target-organ damage, termed hypertensive emergencies. The rate and magnitude of any increase in BP may be more important than the absolute level of BP in determining the severity of organ injury; this is key in obstetric medicine, where the usual BP in younger women may be verging on hypotensive (90–110/60–70 mmHg), and pre-eclampsia may develop with a BP over 140/90 mmHg. In all hypertensive emergencies, intravenous antihypertensive medication therapy is indicated to cause rapid reduction of BP, as this is thought to minimize on-going organ damage and prevent or reduce the risk of morbidity and mortality. The timing, magnitude and other considerations related to the management of these conditions are considered in Box 31.7.␣ Referral to specialist care The majority of hypertensive patients are managed in primary care. Apart from the clear indications related to hypertensive emergencies described earlier, there are other reasons to mandate referral to specialist secondary care: ≥3 drugs with uncontrolled hypertension (resistant hypertension). – Young age (