As well as being the first man to run a mile in under 4 minutes, the late Sir Roger Bannister also left a legacy in medicine, with a primary interest in the autonomic nervous system. In 2005, he was presented with the American Academy of Neurology's first ‘lifetime achievement’ award for his work on autonomic disorders. His research is said to have ensured that the autonomic nervous system is ‘no longer a neglected area of medicine, lying forgotten between neurology, cardiology and general medicine’ (Bannister, 2014).
In 2013, Bannister worked in partnership with Christopher Mathias, a professor of neurovascular medicine, to publish the fifth edition of their textbook, Autonomic Failure (Mathias and Bannister, 2013), with comprehensive chapters on subjects such as orthostatic hypotension, cardiac syncope and postprandial hypotension (PPH). After an introduction to the life and work of Sir Roger Bannister himself, each of these clinical conditions has formed a part of this quarterly series on neurocardiology. This fourth and final article focuses on PPH, a fall in blood pressure occurring within 2 hours of eating.
The sections of this article will follow those of a meal, starting with a ‘bite-size’ overview of the key concepts from Bannister and Mathias, summarised from the detailed chapter on the subject in the fourth edition of their textbook (Mathias and Bannister, 1999). The ‘main course’, or the main body of work that they present on the underlying mechanisms and management of PPH, will then be considered. Just as in haute cuisine, many courses can follow the main, so the final section in this article will consider research done since that of Bannister and Mathias.
Bite-size key concepts of postprandial hypotension
The following points summarise the main concepts discussed in the fourth edition of Autonomic Failure (Mathias and Bannister, 1999).
In the fifth edition of the textbook, it was reported that meals consumed at a higher temperature (50°C) induce a modestly greater fall in blood pressure than cooler meals. However, the mechanisms mediating these effects remain to be determined (Mathias and Bannister, 2013).
The main body of work on postprandial hypotension
A fall in calculated peripheral vascular resistance has been demonstrated after a meal (Kooner et al, 1989); non-invasive measurements of the superior mesenteric artery (a major splanchnic vessel) have shown that this is caused by a large increase in splanchnic blood flow.
In a separate graph, Mathias et al (1989) showed that an increase in heart rate, stroke volume and cardiac output was present in participants without PPH after ingestion of a standard meal. They concluded that:
‘In normal subjects, food ingestion results in a number of hormonal, neural, and regional haemodynamic changes, and the release of a variety of pancreatic and gastrointestinal peptides may affect the cardiovascular system either directly or indirectly through modulation of autonomic nervous activity. Following a meal there is a substantial redistribution of blood into the splanchnic circulation as splanchnic blood flow increases to ~20% of total blood volume. In healthy, young subjects the postprandial increase in splanchnic flow is compensated for by compensatory increases in heart rate and sympathetic activity so that there is little, if any, change in systemic blood pressure.’
Insulin is thought to play a key role in postprandial vasodilatation, with the effects being shown in both calf skeletal muscle and the splanchnic circulation, but not in forearm muscle or skin blood flow (Mathias et al, 1987). These effects are independent of changes in blood glucose levels, as they are also observed with an euglycaemic clamp (Mathias and Bannister, 2013).
In PPH, insulin causes splanchnic vasodilatation and lowers blood pressure in the absence of a compensatory increase in sympathetic nerve activity (Mathias and Bannister, 2013). Modest or no changes in heart rate, cardiac output and plasma noradrenaline or adrenaline levels were observed after a meal, but blood pressure was seen to fall within 10–15 minutes of ingestion and decreased by as much as 40% within 60 minutes (Mathias and Bannister, 2013).
That PPH occurs in patients with type 1 diabetes, who are insulin deficient, suggests that other molecules also play a role. Glucagon-like peptide is described as having effects on gastric emptying, heart rate and blood pressure, while endogenous nitric oxide may also be important in the regulation of splanchnic blood flow (Mathias and Bannister, 2013).
In addition to changes in the composition of meals, and the manner in which they are consumed, several drug therapies for PPH have been tested. Caffeine, through its ability to stimulate the sympathetic nervous system, has been shown to prevent PPH, although not consistently (Armstrong et al, 1990). The somatostatin analogue, octreotide, has been shown to be effective through its ability to prevent the postprandial rise in insulin, but hyperglycaemia is a possible side effect of this treatment (Mathias and Bannister, 2013).
Following on from Bannister's work
More recent research has identified novel ways to reduce PPH in certain, less commonly studied patient groups, such as those with gastrostomy feeding and those receiving dialysis. Whether PPH is a risk factor for new cardiovascular disease has also been questioned, and a role for metformin in the management of PPH has been investigated.
PPH in enteral feeding is an uncommonly considered clinical scenario, yet a study in
Japan suggested simple, non-pharmacological methods to minimise its occurrence. The authors urged the adoption of these methods, as PPH can be a risk factor for syncope and falls, as well as cerebrovascular and cardiovascular events (Sato et al, 2018). In this study of 12 older patients receiving enteral feeding (mean age 79.8 years), it was shown that extending the infusion time from 1 hour to 2 hours and avoiding administration of anti-hypertensive medication immediately before commencing the enteral feed reduced PPH considerably. These effects were most evident when both actions were combined, although performing one of the interventions still somewhat prevented PPH (Sato et al, 2018).
The clinical significance of PPH during haemodialysis remains controversial, with both risks and benefits of eating during dialysis being acknowledged (Fotiadou et al, 2020). Benefits include improved caloric intake and nutritional status, as patients on dialysis otherwise risk missing three meals a week during treatment. Meanwhile, risks include provoking PPH during dialysis, which may cause kidney damage and future cardiovascular events. Increasing blood supply to the gastrointestinal circulation may also interfere with the adequacy of the haemodialysis (Fotiadou et al, 2020). Individualised, patient-specific treatment plans are therefore advised.
Whether PPH can predict the development of new cardiovascular disease through highlighting an inadequate cardiovascular response to postprandial splanchnic blood pooling was the focus of recent research by Jang (2020) in South Korea. After controlling for body mass index, hypertension, diabetes mellitus, and blood pressure in 94 older people with no previous history of cardiovascular disease, this prospective study showed that the presence of PPH was associated with the development of cardiovascular disease. This may be important for the surveillance, early diagnosis and treatment of at-risk groups, although larger studies are needed.
Finally, through its actions on postprandial plasma glucagon-like-peptide-1 levels and gastric emptying, metformin has been shown to attenuate PPH in a randomised controlled trial (Borg et al, 2019). Repurposing drugs is not a novel idea; metformin in particular has many pleiotropic effects, leading scientists to call it the ‘aspirin of the 21st century’. Originally introduced as an anti-influenza drug, it has even been explored as one of the drugs to combat COVID-19 (Sharma et al, 2020; Cory et al, 2021).