| disease | Orthostatic Hypotension |
Orthostatic hypotension is a common clinical manifestation of impaired homeostasis, occurring in 15-20% of the general elderly population. Its prevalence increases with age, cardiovascular disease, and elevated baseline blood pressure. Many elderly individuals experience significant blood pressure fluctuations during postural changes, which are closely related to their baseline supine systolic blood pressure levels. Specifically, when the baseline supine systolic blood pressure is highest, the postural drop in systolic blood pressure is most pronounced, with orthostatic hypotension causing a systolic blood pressure decrease of ≥20 mmHg (2.7 kPa) upon standing. Orthostatic hypotension is a significant risk factor for syncope and falls in the elderly, even in those without other evidence of autonomic nervous system dysfunction.
bubble_chart Etiology
There are two clinical manifestations of orthostatic hypotension in the elderly: physiological (part of the normal aging process) and pathological (caused by disease).
Physiological Orthostatic Hypotension In healthy elderly individuals, this type of hypotension exhibits significant daily fluctuations and is associated with age-related increases in blood pressure and an enhanced response to postural changes in plasma norepinephrine. It is often triggered by common hypotensive stressors, such as reduced blood volume, antihypertensive medications, or the Valsalva maneuver during urination. Although generally asymptomatic and fragile, physiological orthostatic hypotension may be sufficient to reduce cerebral blood flow, leading to dizziness or syncope. Prolonged bed rest can further destabilize blood pressure homeostasis, resulting in severe orthostatic hypotension.
Pathological Orthostatic Hypotension This type is often symptomatic and frequently accompanied by postural dizziness or syncope. Acute orthostatic hypotension is most commonly caused by dehydration due to acute sexually transmitted diseases. In younger patients, a marked increase in heart rate upon standing suggests hypovolemia rather than autonomic dysfunction as the cause of orthostatic hypotension. However, in normal elderly individuals, the increase in heart rate is often less pronounced, so tachycardia may not occur even in cases of hypovolemia-induced orthostatic hypotension. A rarer cause of acute orthostatic hypotension is adrenal insufficiency accompanied by hyponatremia and hyperkalemia (Table 1).Patients with chronic orthostatic hypotension often exhibit autonomic nervous system dysfunction, such as a fixed heart rate, urinary incontinence, constipation, anhidrosis, heat intolerance, impotence, and fatigue.
If no cause for hypotension can be identified in a patient with orthostatic hypotension, it may be primary or idiopathic. Pure autonomic failure (previously called idiopathic orthostatic hypotension) is characterized by a low baseline plasma norepinephrine level in the supine position, a progressive increase in norepinephrine levels upon standing, a lower threshold for the pressor response to norepinephrine infusion, and an enhanced pressor response to tyramine even with reduced norepinephrine release from sympathetic nerve terminals. These changes suggest postsynaptic denervation hypersensitivity due to norepinephrine deficiency in sympathetic nerve terminals.
Table 1 Causes of Orthostatic Hypotension
| Systemic Diseases | Dehydration |
| Adrenal Insufficiency | |
| Pure Autonomic Failure | |
| Central Nervous System Diseases | Shy-Drager Syndrome Brainstem Lesions Parkinson’s Disease Myelopathy Multiple Cerebral Infarctions |
| Peripheral and Autonomic Neuropathies | Diabetes Amyloidosis Tabes Dorsalis Paraneoplastic Syndrome Alcohol and Nutritional Disorders |
| Medications | Phenothiazines and Other Antipsychotics Monoamine Oxidase Inhibitors Tricyclic Antidepressants Antihypertensives Levodopa Vasodilators β-Blockers Calcium Channel Blockers |
In patients with Shy-Drager syndrome, the circulating norepinephrine levels are normal, and the response to infused norepinephrine and tyramine is also normal, but the plasma norepinephrine levels fail to rise upon standing. This syndrome is associated with neuronal degeneration in several areas of the central nervous system, including the corticobulbar, corticospinal, extrapyramidal, and cerebellar systems, as well as the intermediolateral columns of the spinal cord. Therefore, Shy-Drager syndrome is a central nervous system disorder affecting sympathetic blood pressure control, often accompanied by extrapyramidal and cerebellar symptoms.
Disorders of the peripheral autonomic nervous system also cause pathological orthostatic hypotension. These include insulin-dependent diabetes mellitus, which leads to severe peripheral neuropathy and other end-organ damage; less common causes are amyloidosis, vitamin deficiencies, and neuropathies associated with malignancies, particularly lung cancer and pancreatic cancer.
The most common cause of orthostatic hypotension is likely the use of medications, such as phenothiazines, tricyclic antidepressants, anxiolytics, and antihypertensive drugs. The latter include centrally acting agents (e.g., methyldopa and clonidine) and peripherally acting agents (e.g., prazosin, hydralazine, and guanethidine). Due to the age-related impairment of ventricular diastolic filling, older adults rely on adequate venous return to maintain normal cardiac output. Therefore, medications that reduce venous return, particularly nitrates and diuretics, often cause orthostatic hypotension. Many drugs can induce orthostatic hypotension in the elderly even at conventional doses.
bubble_chart Diagnosis
When elderly patients complain of positional dizziness and grade I confusion, clinicians should not immediately assume they have orthostatic hypotension. First, have the patient lie flat for at least 5 minutes to measure blood pressure and pulse rate, then measure again after standing quietly for 1 minute, and continue standing for 3 minutes before taking another measurement. Hypotensive reactions may occur immediately or be delayed after standing. To detect delayed hypotensive reactions, prolonged standing or tilt-table testing may be necessary. Before initiating treatment, blood pressure should be measured multiple times to confirm the persistent presence of orthostatic hypotension.
bubble_chart Treatment Measures
Symptomatic patients should not take antihypertensive medications before meals and should lie flat after meals. Reducing the dose of antihypertensive drugs and adopting a small, frequent meal approach may also help. Recent data suggest that in some patients, walking after meals may aid in restoring normal circulation, but this therapy should only be implemented under close monitoring.
Studies on patients with autonomic dysfunction have shown that indomethacin 50mg every 6 hours, caffeine 250mg with or without dihydroergotamine 6–10mg/kg subcutaneously or somatostatin 12–16mg subcutaneously before meals may improve postprandial hypotension. Caffeine should only be administered in the morning so its effects wear off by evening, to avoid disrupting the patient's sleep and prevent drug tolerance.
