René W. M. M. Jansen

Postprandial Hypotension: Epidemiology, Pathophysiology, and Clinical Management

Postprandial hypotension was first recognized as a clinical problem in 1977 in a patient with Parkinson disease [1]. However, the hypotensive effect of meal ingestion has been appreciated for a longer time. In 1935, Gladstone [2] described a hypertensive patient who had had a postprandial decrease in blood pressure from 185/120 mm Hg to 145/80 mm Hg. In 1953, Smirk [3] observed a decrease in blood pressure after patients with autonomic failure ingested food. Robertson and colleagues [4] confirmed these results in patients with chronic autonomic failure and found an average decrease in systolic blood pressure of 49 6 mm Hg after a meal [4]. Since Lipsitz and colleagues [5] first described it in nursing home residents a decade ago, postprandial hypotension has become recognized as a common disorder of blood pressure regulation in the elderly [5]. Our current understanding of postprandial hypotension is limited by the lack of a standardized, clinically meaningful definition. Analogous to orthostatic hypotension, postprandial hypotension is commonly defined in the literature as a decrease in systolic blood pressure of 20 mm Hg or more within 2 hours of the start of a meal. Postprandial hypotension also develops when the absolute level of systolic blood pressure after a meal decreases to less than 90 mm Hg and when the systolic blood pressure before a meal is greater than 100 mm Hg. In addition, if a meal-related decrease in systolic blood pressure exceeds the threshold for cerebral autoregulation, patients may become symptomatic when the absolute systolic blood pressure level exceeds 90 mm Hg or when the postprandial systolic blood pressure decreases to less than 20 mm Hg. The frequent absence of symptoms associated with this decrease in blood pressure after meal ingestion makes the value of this definition uncertain. In addition, the morbidity and mortality related to postprandial hypotension are unknown. A potential cumulative effect of multiple hypotensive stresses, such as posture change or administration of medication at the time of meal ingestion, makes assessment of the clinical relevance of individual blood pressure responses to a meal even more difficult. Although it can be exacerbated by posture change, postprandial hypotension is a distinct entity that differs from orthostatic hypotension. We have reviewed the current knowledge of the epidemiology, clinical symptoms and significance, pathophysiology, and management of postprandial hypotension. We hope to make the practicing physician more aware of this common abnormality in blood pressure regulation and to stimulate new research of its mechanisms and management. Methods Through a MEDLINE search, we identified all articles on postprandial hypertension published between 1966 and 1994. We also used the bibliographies of relevant articles. All articles and case reports describing meal-related hypotension in the elderly and in patients with autonomic failure were included for analysis. Epidemiology and Associated Conditions During the past decade, hypotension in response to ingestion of a mixed meal or oral glucose has been shown in healthy elderly persons [6-14]; young and elderly persons with hypertension [10, 15-21]; elderly patients in nursing homes [5, 22-25]; and patients with postprandial syncope [26, 27], autonomic insufficiency [4, 28-36], Parkinson disease [1, 37-39], paraplegia [40], diabetes mellitus [28, 38, 41], cardiovascular disease [42, 43], and renal failure treated with hemodialysis [44, 45]. However, the epidemiology of postprandial hypotension has not been thoroughly studied. Mild, meal-induced decreases in blood pressure are common in healthy older persons [6-11], but the prevalence of these decreases is unknown. The presence of multiple illnesses in elderly persons may further impair cardiovascular adaptation to meal ingestion and result in marked postprandial decreases in blood pressure. Investigations of elderly persons living in nursing homes have shown that nearly all persons experience some decrease in blood pressure [24, 25]. In 24% to 36% of these patients, systolic blood pressure decreases more than 20 mm Hg within 75 minutes of eating a meal [24, 25]. It has been difficult to dissociate the effects of physiologic aging on postprandial blood pressure regulation from those of age-associated illnesses. The elevation in blood pressure associated with aging can profoundly influence postprandial blood pressure. In a study of 82 healthy persons aged 19 to 79 years, meal-related reductions in supine systolic and diastolic blood pressure were significantly correlated. However, when the data were corrected for baseline blood pressure, this correlation was no longer seen [46]. Older hypertensive persons have greater reductions in blood pressure after ingesting food or oral glucose than do age-matched normotensive persons [7, 9, 10, 17-20]. Postprandial decreases in systolic blood pressure ranging from 17 to 25 mm Hg have been found in hypertensive elderly patients older than age 65 years who did not have other overt cardiovascular diseases [9, 10, 17, 18]. In these patients, diastolic blood pressure may decrease as much as 15 mm Hg. However, because hypertensive middle-aged and young persons also have postprandial decreases in blood pressure [10, 16], this phenomenon may be primarily caused by blood pressure elevation rather than by aging itself. Profound postprandial hypotension has been observed in patients with autonomic failure [1, 4, 28-36, 47, 48]. The first case report described a 65-year-old man who had dizziness and visual disturbance associated with large decreases in blood pressure after almost every meal [1]. Robertson and colleagues [4] found a marked postprandial decrease in sitting systolic blood pressure (range, 22 to 98 mm Hg) in 10 patients with autonomic failure. Hoeldtke and associates [28, 47] studied patients with multiple-system atrophy (the Shy-Drager syndrome) and pure autonomic failure and found that the decrease in the mean sitting postprandial arterial blood pressure ranged from 62 to 83 mm Hg [28, 47]. All of these patients had blurred vision and dizziness after the meal [47]. Postprandial hypotension is also commonly found in patients with peripheral neuropathy caused by diabetes mellitus or other disorders [28, 33, 38, 41] as well as by Parkinson disease [1, 37-39]. Hypotension is a common side effect of antiparkinsonian drugs such as levodopa. In patients with renal failure, symptomatic postprandial hypotension has been seen during hemodialysis [44, 45]. This appears to be relevant primarily in uremic patients who have autonomic dysfunction. Determining the prevalence and clinical implications of postprandial hypotension is complicated not only by different diseases and drugs in the populations studied but also by methodologic inconsistencies among studies. First, the bodys position while the meal is being consumed probably affects food-induced changes in blood pressure. Postprandial hypotension occurs both in the sitting and supine positions. Although the sitting position is more physiologic, orthostatic changes in blood pressure during prolonged sitting might contribute to the postprandial decrease in blood pressure. Second, no studies have addressed the variability of postprandial blood pressure. Previous studies have shown that orthostatic blood pressure measurements in the elderly vary considerably from day to day [49]. This could also be true for postprandial hypotension. Third, the nutrient composition of meals affects the magnitude of the decrease in postprandial blood pressure [12, 13, 15, 50]. Carbohydrates and, more specifically, glucose have been found to play a significant role [10, 29]. However, conflicting data have been reported about the influence of fat or protein on postprandial blood pressure [12, 13, 15, 51, 52]. Fourth, postprandial hypotension depends on the temperature of the meal [53]. After cold glucose solutions are ingested, blood pressure remains unchanged, whereas glucose solutions served warm or at room temperature cause a decrease in blood pressure. Finally, the time at which blood pressure is measured after a meal may influence the detection of this phenomenon. Postprandial hypotension can be found at all meal times [14] and is almost immediately apparent after a meal. Blood pressure usually reaches a nadir within 30 to 60 minutes. In nursing home residents, the systolic blood pressure nadir occurred as early as 15 minutes after the meal in 13% to 17% of the patients and as late as 75 minutes after the meal in 11% to 13% of the patients [24, 25]. Clinical Symptoms and Significance In elderly persons or patients with autonomic failure, postprandial reductions in blood pressure may result in syncope, falls, angina pectoris, weakness, dizziness, nausea, lightheadedness, or black spots in the visual field [1, 5, 22, 24-26, 29, 39, 46] (Table 1). In addition, case reports have described elderly patients with large postprandial reductions in blood pressure who developed angina pectoris or transient ischemic attacks that resolved as blood pressure returned to normal [24, 54]. However, data on the frequency of postprandial hypotension and its potential symptoms are scarce. In one recent study, half of a group of patients with unexplained syncope had postprandial hypotension [27]. Table 1. Clinical Symptoms Associated with Postprandial Hypotension The cerebral symptoms probably depend on the extent to which cerebral perfusion is compromised. Accumulation of age- and disease-related conditions that threaten cerebral blood flow or reduce oxygen content in the blood may bring cerebral oxygen delivery near the threshold needed to maintain consciousness [55]. Therefore, even small changes in blood pressure may reduce cerebral oxygen delivery to below the critical threshold and thus result in ischemic symptoms. The potential for postprandial cerebral ischemia may be greater in elderly p

Intraindividual reproducibility of postprandial and orthostatic blood pressure changes in older nursing-home patients : Relationship with chronic use of cardiovascular medications

OBJECTIVES: Although postprandial and orthostatic hypotension are commonly observed in nursing home residents, their reproducibility, relationship to each other, and association with chronic use of cardiovascular medications are poorly understood.

Amyloid beta protein and tau in cerebrospinal fluid and plasma as biomarkers for dementia: a review of recent literature.

This review addresses recent developments in amyloid beta (Abeta), total tau (t-tau), and phosporylated tau (p-tau) protein analysis, in cerebrospinal fluid (CSF) and plasma as biomarkers for dementia. Recent research focused on the protection of patients with mild cognitive impairment (MCI) into dementia and the differential diagnosis of Alzheimers Disease (AD). A combination of Abeta42 and t-tau in CSF can discriminate between patients with stable MCI and patients with progressive MCI into AD or other types of dementia with a sufficient sensitivity and specificity. Regression analyses demonstrated that pathological CSF (with decreased Abeta42 and and increased tau levels) is a very strong predictor for the progression of MCI into AD. Furthermore, CSF measurements of p-tau and Abeta42 can assist in diagnosing vascular dementia or frontotemporal dementia in the differential diagnosis of AD indicated by a reasonable sensitivity and specificity. Whether tau in combination with Abeta42 or in combination with the Abeta37/Abeta42 or Abeta38/Abeta42 ratio aids in the discrimination between AD and Lewy Body dementia remains to be elucidated. Cross-sectional research could not demonstrate significant differences for Abeta40 and Abeta42 in plasma between AD and controls. However, a recently published longitudinal study showed high baseline Abeta40 levels, especially when combined with low baseline Abeta 42 levels, are a strong risk factor for the development of dementia. This emphasizes the importance of performing longitudinal studies in addition to cross-sectional ones. The origin of plasma Abeta and its transport between CSF and plasma, however, needs further clarification. In conclusion, progress has been made regarding Abeta and tau as biomarkers for dementia, both for differentiation between stable MCI and progressive MCI patients and for the differential diagnosis of AD. Future research should aim to validate these recently published results, preferably in pathologically confirmed AD patients. In addition, it is important to standardise research in terms of study design (longitudinal, minimal follow-up period of 5 years), type of researched parameters ( total or p-tau, type of Abeta peptides), type of matrix (CSF and plasma) and data analysis (establishment of predefined cut-off values, type of ratio, type of marker combination).

The Influence of Age and Blood Pressure on the Hemodynamic and Humoral Response to Head-Up Tilt

It has been reported that postural hypotension in the elderly is common. However, these studies included institutionalized and more or less disabled persons. Furthermore, postural hypotension may be related to baseline blood pressure. In this study, the influence of age and blood pressure on the hemodynamic and plasma catecholamine responses to orthostatic stress was investigated in young and old normotensive and hypertensive healthy subjects. In normotensive and hypertensive elderly persons, the percentage blood pressure responses during tilt were not significantly different from that seen in young normotensives. We measured a slight decrease of systolic blood pressure and a slight increase of diastolic blood pressure. The hypertensive young patients showed an enhanced diastolic blood pressure response with no fall in systolic blood pressure, in contrast to the normotensive young subjects. Both elderly groups had a lower increase of heart rate than the young subjects. The percentage increase in norepinephrine after tilting was significantly lower in elderly hypertensives than in elderly normotensives and young hypertensives. The presence of hypertension was associated with a decrease in blood pressure, but age had no influence on the change in blood pressure during tilt. In this group of healthy elderly subjects, there was no significant orthostatic hypotension when the blood pressure course of the entire tilt test was taken into account.

The Influence of Food Temperature on Postprandial Blood Pressure Reduction and Its Relation to Substance-P in Healthy Elderly Subjects

Blood pressure (BP) in the elderly may decrease after a meal or oral glucose loading. The mechanism of this phenomenon is still unclear. In addition, the effect of the temperature of a meal on postprandial BP is unknown. However, it has been suggested that vasoactive gastrointestinal peptides are involved in the etiology of postprandial BP reduction. Therefore, we studied the effects of a cold and a warm glucose solution on BP, heart rate, plasma glucose, insulin, and substance‐P levels in 15 healthy elderly subjects with a mean age of 74 ± 3 (SD) years. With an interval of at least 2 days, a warm (50° C) and a cold (5° C) solution (75 g glucose/300 mL water) were given in random order. After the cold glucose loading mean arterial pressure increased by a maximum of 3.9 ± 1.3 mmHg (P < 0.01). In contrast, BP decreased after the warm solution by a maximum of 8.0 ± 1.1 mmHg (P < 0.001). Neither test had an influence on plasma substance‐P levels. Our data suggest that postprandial blood pressure reduction in the elderly is dependent on food temperature. Substance‐P does not seem to play a role in this phenomenon.

Neurohormonal effects of furosemide withdrawal in elderly heart failure patients with normal systolic function

In heart failure patients, diuretics cause renin–angiotensin–aldosterone system (RAS) activation, which may lead to increased morbidity and mortality despite short‐term symptomatic improvement.

Cortical Oxygen Supply During Postural Hypotension is Further Decreased in Alzheimer's Disease, but Unrelated to Cholinesterase-Inhibitor Use

Cerebrovascular function and structure of the cortical cerebral microvessels are profoundly altered in patients with Alzheimers disease (AD). The functional hemodynamic consequences of such changes, however, remain essentially unknown. Cholinesterase inhibitors (ChEIs) potentially affect brain perfusion through either augmentation or inhibition of cerebral vasodilatation. This study investigated the cerebrovascular regulation during postural changes in AD before and after treatment with the ChEI galantamine. In 21 AD patients and 20 controls, blood pressure (BP--Finapres), frontal cortical oxygenation (near-infrared-spectroscopy), and cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography) were measured following a hypotensive challenge induced by postural change. In AD, measurements were repeated after 10 (SD 4) weeks of galantamine. Baseline cerebrovascular resistance was higher in AD (AD 2.83 (0.87) mmHg/cm/s, control 2.24 (1.3) mmHg/cm/s, p=0.010). 13 AD patients and 17 controls had a sufficiently large postural drop in BP (> 10 mmHg). AD patients had a larger postural decline in the frontal cortical concentration of total hemoglobin (Delta [tHb] AD=1.03 (0.70) micromol/l, control =0.30 (0.90) micromol/l, p=0.015). Moreover, the reduction in oxygenated hemoglobin was 57% larger in AD (p=0.085). Unexpectedly, the postural changes in BP were smaller in AD. Galantamine treatment affected neither orthostatic BP nor the decrease in [tHb]. In conclusion, even for moderate orthostatic hypotension during commonly occurring postural changes, cerebral cortical tissue perfusion declined more in AD, suggesting increased ischemic vulnerability of the brain. Galantamine neither improved nor impaired cerebrovascular regulation.

The Influence of Oral Glucose Loading on Baroreflex Function in the Elderly

Blood pressure in the elderly may decrease after a meal or after oral glucose loading. It has been suggested that eating may affect blood pressure homeostasis through an insulin‐induced blunting of baroreflex sensitivity. We investigated the effects of oral glucose loading on baroreflex sensitivity in young normotensives and in elderly normo‐ and hypertensive subjects. Blood pressure was measured by a new noninvasive device, Finapres, which measures blood pressure continuously in the finger. Baroreflex sensitivity was estimated with the phenylephrine and nitroglycerin method. In both elderly groups mean arterial pressure fell significantly after the glucose load (11 ± 1 mm Hg, P < .001 in the hypertensives, and 8 ± 2 mm Hg, P < .01 in the normotensive subjects), whereas no change in blood pressure was found in the young group. Baroreflex sensitivity was lower in both elderly groups than in young normotensives. Glucose loading had no influence on baroreflex sensitivity in the three groups. Therefore, we conclude that other factors are involved in the phenomenon of postprandial hypotension in the elderly. J Am Geriatr Soc 37:1017–1022, 1989

Diuretic Therapy in Elderly Heart Failure Patients With and Without Left Ventricular Systolic Dysfunction

Long term prescription of diuretics for heart failure is very prevalent among elderly patients, although the rationale for such a treatment strategy is often unclear, as diuretics are not indicated if volume overload is absent. The concept of diastolic heart failure in the elderly might particularly change the role of diuretic therapy, since diuretics may have additional adverse effects in these patients. This paper reviews the effects of diuretic therapy in elderly patients with heart failure, emphasising the differences between patients with normal and decreased left ventricular systolic function. Studies on diuretic withdrawal in elderly patients with heart failure are discussed, with emphasis on issues involved in decision making such as diuretic dose reduction and withdrawal in elderly patients and factors that have been established to predict successful withdrawal. Existing guidelines on the prescription of diuretics in elderly patients with heart failure with normal and decreased left ventricular systolic function and in those with diastolic heart failure are also discussed. By reducing intravascular volume, diuretics may further impair ventricular diastolic filling in patients with diastolic heart failure and thus reduce stroke volume. Indeed, preliminary studies demonstrate that diuretics may provoke or aggravate hypotension on standing and after meals in these patients. Therefore, it is suggested that elderly patients with heart failure with intact left ventricular systolic function should not receive long term diuretic therapy, unless proven necessary to treat or prevent congestive heart failure. This implies that physicians should carefully evaluate the opportunities for diuretic dose tapering or withdrawal in all of these patients, and that a cautiously guided intermittent diuretic treatment modality may be critical in the care for older patients with heart failure with intact left ventricular systolic function.

Effects of furosemide versus captopril on postprandial and orthostatic blood pressure and on cerebral oxygenation in patients ≥70 years of age with heart failure

Elderly patients with heart failure are at risk of postprandial hypotension (PPH), orthostatic hypotension (OH), and concomitant cerebral oxygenation changes because of altered cardiovascular balance and the use of cardiovascular medications, such as furosemide and captopril. In 24 patients with heart failure (New York Heart Association class II to III, in stable condition, and receiving cardiovascular medication [aged 70 to 83 years]), blood pressure (BP) was measured by Finapres, and cortical concentrations of oxyhemoglobin and deoxyhemoglobin were measured using near-infrared spectroscopy during standing and after a 292-kcal carbohydrate meal. Tests were performed before and during therapy with furosemide 40 mg once daily (n = 11) or captopril 6.25 and 12.5 mg twice daily (n = 13) in a double-blind randomized trial. Before treatment, 13 of 24 patients had PPH, and 2 of 24 patients had OH. The first dose of furosemide significantly decreased postprandial systolic BP (p <0.05) and postprandial frontal cortical oxygenation (p <0.05), whereas the first dose of captopril did not. Furosemide and captopril did not significantly affect postprandial or orthostatic BP or cortical oxygenation after 2 weeks of treatment. Thus, PPH is a common phenomenon in elderly patients with heart failure, whereas OH is not. The first dose of furosemide 40 mg decreased postprandial systolic BP and frontal cortical oxygenation, in contrast with the first dose of captopril 6.25 mg and 2-week treatment with furosemide 40 mg once daily or captopril 12.5 mg twice daily. These findings indicate that initiating furosemide treatment worsens PPH, and furosemide is less safe in elderly patients with heart failure.