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systolic hypertension studies used systolic BP treatment targets of 160 or 150 mmHg.718 However, results from the SPRINT and the Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trials (mean BP at study entry of 140/78 mmHg and 146/82 mmHg, respectively, indicating that many of the patients had isolated systolic hypertension) confirm that lower systolic BP targets are effective in reducing CVD events in patients with isolated systolic hypertension (see Supplementary data online).135,136 Since relative risk reduction by BP-lowering treatment is homogeneous in any age group, whereas absolute risk reduction is larger with advancing age,131 therapeutic inertia in older patients with isolated systolic hypertension should be avoided (see Section 9.3). As noted earlier, beta-blockers should be avoided in patients with isolated systolic hypertension or more generally with arterial stiffness, as they increase stroke volume (given the lower heart rate).218

9.4.3 Isolated systolic hypertension in young adults

In young adults (<40 years old), the presence of isolated systolic hypertension poses different pathophysiological and clinical considerations. In young patients with isolated systolic hypertension, arterial stiffness713 and relative risk of CVD events624 appear to be similar to those without isolated systolic hypertension and lower than young adults with combined systolic-diastolic hypertension and isolated diastolic hypertension. Indeed, younger patients with isolated systolic hypertension appear to comprise a heterogeneous group.719 For these reasons, it might be reasonable to assess central BP and arterial stiffness in these individuals, as recommended by other scientific societies.720,721 Out-of-office BP measurement is recommended to exclude white-coat hypertension, which is often associated with isolated systolic hypertension in the young.634

9.4.4 Isolated diastolic hypertension

Isolated diastolic hypertension is defined as a systolic BP of <140 mmHg with a diastolic BP of ≥90 mmHg. The isolated diastolic hypertension phenotype is more commonly seen in younger adults and, particularly, younger adults with obesity or other metabolic derangements.722,723 In older adults with this phenotype, consideration should be given to whether the diastolic BP was accurately measured.724 Patients with isolated diastolic hypertension appear to have a slightly increased relative risk for CVD of 5%–30%.548,723,725 However, because patients with isolated diastolic hypertension are younger, they tend to have few events, and very large samples are required to show this association. Furthermore, because the absolute risk for CVD among these individuals is low (typically <10% over 10 years), it is less clear if isolated diastolic hypertension should prompt initiation of BP-lowering medication, particularly among persons in whom baseline systolic BP is already at the target of 120–129 mmHg.723 Irrespective, patients with isolated diastolic hypertension should be followed up, as they are at increased risk for systolic hypertension.723 Finally, it is also worth noting that when a patient achieves a target systolic BP of 120–129 mmHg with BP-lowering treatment, there is little to no high-quality trial evidence that further intensifying BP-lowering medication to achieve both systolic BP of <120 mmHg and also diastolic BP of <70 mmHg improves CVD prognosis.547,723

9.5 Orthostatic hypotension with supine

hypertension Patients with orthostatic hypotension need not be hypotensive and indeed, many have supine elevated BP or supine hypertension. Furthermore, many patients with orthostatic hypotension are asymptomatic. Orthostatic hypotension is present in around 10% of all adults with hypertension and is defined as a drop in BP of ≥20/10 mmHg after rising from either a sitting or lying position to a standing position (see Section 5.5.3).97,99 Assessment for orthostatic hypotension should be timed to occur at 1 and/or 3 min after standing. Because seated to standing assessment can lead to under-detection of orthostatic hypotension, it is preferable, where possible, to test for orthostatic hypotension using a supine (lying) to standing assessment (see Section 5).56,98,726

Assessing for orthostatic hypotension is important in managing adults with elevated BP or hypertension for several reasons. First, findings of trials linking more intensive BP control to improved outcomes may not generalize to patients with orthostatic hypotension, particularly when it is severe in magnitude (standing systolic BP < 110 mmHg97) and/or symptomatic. Second, orthostatic hypotension may be associated with symptoms that may limit the patient’s tolerability of more intensive BP-lowering approaches. Third, orthostatic hypotension may be associated with an increased risk of adverse effects commonly co-attributed to pharmacological BP lowering (such as hospitalizations for hypotension).727 Fourth, orthostatic hypotension is associated with increased risk for CVD.728 However, the frequency of orthostatic hypotension is not increased in the more intensive BP-lowering arms of randomized trials compared with the less intensive BP-lowering arms.726,727,729,730 As such, and in contrast to common belief, it does not appear that more intensive treatment of BP (which almost always requires more BP-lowering medication) worsens orthostatic hypotension. In contrast, there is some evidence that more intensive treatment of hypertension may actually reduce the risk of orthostatic hypotension.730,731 The aetiology of orthostatic hypotension may be considered as neurogenic or non-neurogenic, with the latter being far more common.99 Patients with orthostatic hypotension may have underlying neurodegenerative diseases, diabetes, B12 deficiency,732 renal failure, dehydration, prolonged recumbency, deconditioning, and triggering medications (like alpha-blockers, beta-blockers, diuretics, nitrates, antidepressants, and antipsychotics). Of note, ACE inhibitors, ARBs, and dihydropyridine CCBs are examples of BP-lowering medications that appear to have less impact on orthostatic hypotension, and their adverse impact, if any, on orthostatic hypotension typically occurs in the first 2 weeks or so after starting or intensifying treatment.733 Managing patients with supine hypertension and orthostatic hypotension is a common clinical conundrum. More detailed reviews on this topic are available elsewhere.98,99 The approach to managing orthostatic hypotension should be non-pharmacological at first. Patients with orthostatic hypotension should be asked to change position slowly, maintain adequate hydration, and avoid alcohol and large meals. Compression stockings, crossing legs while standing, and abdominal binders may also help and should be trialled.734,735 Abdominal heating pads and a head-up bed position can reduce supine (typically nocturnal) hypertension, which may reduce nocturnal diuresis and daytime orthostatic hypotension.736 The treatment of orthostatic hypotension among those with supine hypertension is not to automatically down-titrate BP-lowering medications. Rather, reversible causes should be sought and treated (including discontinuation of offending medications), and patients requiring BP-lowering medication should be switched to BP-lowering medications that are less likely to cause orthostatic hypotension. When symptoms are disabling and the above interventions do not help, particularly in neurogenic orthostatic hypotension, the best evidence exists for midodrine to reverse orthostatic hypotension, and this may be given in conjunction with ongoing BP-lowering medications when supine hypertension exists.99 An alternative option to midodrine is droxidopa, though this is less readily available. Specialist referral is prudent when persons with supine hypertension are prescribed these orthostatic hypotension treatments, as these agents can increase supine BP more than standing BP. Downloaded from academic.oup.com/eurheartj/article/45/38/3912/7741010 by guest on 07 October 2026