Hypertension - Clinical and Historical Significance for Psychiatry

 

 

I have written about hypertension in the past on this blog. During the treatment and ongoing care of the many patients I have seen over the years it is always present. The prevalence of hypertension increases with age and other comorbidities. The case of the patients I have seen alcohol and other substance use, obesity, smoking, stress, and prescribed medications are all risk factors. As a psychiatrist following blood pressures, I have to be more compulsive than the average physician. I have rarely been in an outpatient clinic where blood pressures were routinely checked. On the inpatient units where I have worked, blood pressure monitoring could also be a problem. I am reminded of teaching in services on blood pressure monitoring. In inpatient settings is also fairly common to see patients admitted who have discontinued antihypertensive therapy and developed dangerously high blood pressures. In many of those cases they continued to refuse the medication. I was put in the uneasy position of having to follow extremely high blood pressures until a probate court judge could convince the patient it was in their best interest to take those medications.

I have also seen the long-term consequences of uncontrolled hypertension in the form of acute hemorrhagic strokes, subarachnoid hemorrhages, aortic aneurysms, hypertensive cardiomyopathy, and the variations of hypertension related dementia. Many of these findings were in the context of an acute emergency. Several were more of an unexpected finding such as the likely long-term consequences of eclampsia and a brain imaging study done 30 years later.

In the day-to-day care of patients, knowing whether or not they may have hypertension is a critical aspect of care. That is true whether you are considering a medication that can elevate or decrease blood pressure, advising the patient on lifestyle changes to improve their health, or discussing their current exercise program. Most people are unaware of the acute effects of exercise on blood pressure and why strenuous exercise may be contraindicated until they have adequate control of blood pressure.

For all of these reasons, I am always interested in when new guidelines come out or blood pressure screening. Over the years that I have been practicing the suggested cutoffs demarcating hypertension and ranged anywhere from 120/80 to [Age + 100]/90. The [Age + 100]/90 cutoff was a guideline we used when I was an intern in the 1980s. That meant that if you are treating a 70-year-old their acceptable blood pressure was a maximum of 170/90. Over the years extensive research has examined blood pressure dependent outcomes and determined that systolic blood pressures that high are problematic. The question is always-where is the cutoff? Specifically at what point are we maximizing the gains and reducing the risks from overtreatment and using excessive diagnostics. 

The question is one that the US Preventive Services Task Force (USPSTF) seeks to answer. They published their comprehensive look at the issue recently (1).  Hypertension prevalence of 45% of all adults in the US is noted as well as the morbidity and mortality associated with untreated hypertension.  The quoted range of cutoffs is from 130/80 to 140/90. The technical considerations of blood pressure determinations are discussed. Suggested sensitivity of 0.8 and specificity 0.55 for office blood pressure measurement (OBPM) and 0.84 and 0.6 for home blood pressure measurement (HBPM).  Review of 13 study showed that the harms of blood pressure screening are minimal. 

The standard online medical text in the US is UpToDate and it defines hypertension as <120 mmHg systolic and <80 mmHg diastolic with Stage 1 hypertension being 130-139 mmHg systolic and 80-89 mmHg diastolic.  Stage 2 hypertension is defined as systolic of 140 mmHg and diastolic of 90 mmHg. UpToDate also defines a category of treated hypertension for any patient taking antihypertensive medication irrespective of their blood pressure reading. 

The USPSTF paper had an interesting section called How Does Evidence Fit with Biological Understanding? This did not involve a discussion of pathophysiology, but the description of subtypes and what the implications might be.  Sustained hypertension was defined as elevated blood pressure determine both in the office and outside of office settings. Whitecoat hypertension was defined as elevated blood pressure in the office but not in ambulatory settings. Masked hypertension was defined as elevated blood pressure outside of the office but not in office settings. For the purposes of the document, sustained hypertension is considered the entity that the recommendations are based on and the overall risk of cardiovascular disease is sustained hypertension > masked hypertension > whitecoat hypertension.  The diagnosis of white coat hypertension is made by comparing OBPM with HBPM or ABPM (ambulatory blood pressure measurement).  No specific biological mechanisms are discussed. The document points out that even though masked hypertension and whitecoat hypertension are associated with adverse cardiovascular outcomes there is no current evidence that treatment improves as outcomes and they consider that to be a knowledge gap.

UpToDate take a more detailed look at primary and secondary hypertension but does not elaborate much more on the pathogenesis and biology of hypertension. For example, it outlines the autonomic nervous system, the renin aldosterone system, and total plasma volume as being the main systems involved in hypertension. Secondary causes and screening for these causes is suggested but there are no confirmatory tests for essential hypertension.  Interestingly atypical antipsychotics and antidepressants are on a list of medications thought to contribute to hypertension but in personal correspondence with a hypertension specialist – he considered even the most likely medications in that category (bupropion and venlafaxine) to be rare causes.  Empirical treatment and how to treat more resistant forms of hypertension are reviewed. The medications typically address a purported mechanism of hypertension but there is no suggestion to determine the underlying physiology and match it with a medication effect.

Monitoring is another role that psychiatrists can fill. I see the same patient ranging from 6 to 24 visits per year and ideally those would all be heart rate and blood pressure data points. With many of those patients I also discuss home monitoring since approved devices are now very affordable and many of them are being treated often intermittently for hypertension. It is also critical that some patients are able to do HBPM if they are treated with medications that can clearly affect blood pressure such as beta-blockers, prazosin, and clonidine. For subgroup of people who have sustained tachycardia who need close monitoring I also recommend HBPM.

Every psychiatrist should be aware of both the USPSTF screening guideline and either the UpToDate chapter or a similar comprehensive book chapter or review.  Making sure that the patients in question get adequate screening, evaluation, and treatment is as critical as the treatment for their psychiatric disorder.  Comorbidities that are the direct result of end organ damage from hypertension also need to be addressed. I have been able to advise patients on dietary changes, exercise programs, and accepting treatment for obstructive sleep apnea when it was ignored from other sources.

Apart from the medical and clinical considerations of hypertension – are there any other lessons for psychiatry?  It turns out there are and they were first noted in 1960 and since forgotten.  Until that year there was a predominance of the view that diseases are caused by discrete pathological lesions. That view was advanced by Virchow and Koch and was the predominant view of the day. A corollary is that there are always qualitative differences between health and disease.  If a person has the required lesion, they have the disease and if not, they are healthy. That theory was disrupted by a paper by Oldham, et al (3) on the nature of essential hypertension. At that time, the dominant theory of hypertension was that it was an autosomal dominant determined disease that “separately sharply” from the normotensive population. The authors looked at collected data on families and showed that the percentage of families in previous generations with hypertension was too low for Mendelian inheritance.  The authors looked at data on the blood pressure ranges of first-degree relatives of their index hypertensives. The graphical data was interpreted as bimodal distribution of blood pressures consistent with a clear demarcation between elevated blood pressure and normotension.  However, re-examination of the data and a further trial showed that the frequency distribution of blood pressures was not consistent with a bimodal distribution or as the author’s state:

 “seems to illustrate once again that it is not hypertension that is inherited but the degree of hypertension.”

The authors use this data to reject a dominant gene and qualitative differences between disease and non-disease state.  They go on to describe the biological implausibility:

“The alternative hypothesis-that arterial pressure is inherited polygenically over the whole range, and that the inheritance is of the same kind and degree in the so-called normal range as in that characteristic of essential hypertension-is in general conformity with biological theory and with the facts of observation. Just as stature, the classical human example of polygenic inheritance, is the sum of a number of separate bones and tissues, so is the arterial pressure the resultant of a number of discrete components of the cardiovascular system. One need only mention the radii of different parts of the vascular system, the lengths of the vessels constituting the resistance, their elasticity, the chemical composition.”  p. 1092.

As I read that passage, I was reminded of current work looking at the tens to hundreds of network genes activated across the genotypes of millions of unique individuals as a basis for the polygene events that occur in polygenic disorders including psychiatric disorders.

Once the polygene quantitative model was accepted over the single dominant gene qualitative model, it led to a broader application including the obvious one to psychiatric disorders.  Psychiatric disorders have been demonstrated to have familial patterns and some have a very high degree of heritability, but they also do not follow single dominant gene inheritance.  To recap, Oldham, et al basically blew the single gene, qualitative difference between disease state and normality, single pathological mechanism out of the water for complex disorders and they did it in 1960! No philosophy or rhetoric – just good old science. At one point the authors point out that “no student of genetics” had explained the dips in the hypertension frequency graphs.

The psychiatric significance of these authors’ work occurs when Kendell (4) highlighted it 15 years later to illustrate why the single pathological mechanism as “proof” of psychiatric disease is a failure.  Hypertension is a complex polygenic disorder that all psychiatrists must concern themselves with if they are actively treating patients.  It is also a useful comparison model for the psychiatric disorders that we treat,

 the body fluids, the action of the heart, and the

 George Dawson, MD, DFAPA

 

References:

1:  US Preventive Services Task Force, Krist AH, Davidson KW, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Kubik M, Li L, Ogedegbe G, Pbert L, Silverstein M, Stevermer J, Tseng CW, Wong JB. Screening for Hypertension in Adults: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2021 Apr 27;325(16):1650-1656. doi: 10.1001/jama.2021.4987. PMID: 33904861.

2:  Basile JM, Bloch MJ. (2021) Overview of Hypertension in Adults. In GL Bakris, WG White, GP Forman, L Kunins, UpToDate (Accessed 4/28/2021) from:  https://www.uptodate.com/contents/overview-of-hypertension-in-adults

3:  Oldham PD, Pickering G, Fraser Roberts JA, Sowry GS. The nature of essential hypertension. Lancet. 1960 May 21;1(7134):1085-93. doi: 10.1016/s0140-6736(60)90982-x. PMID: 14428616.

4:  Kendell RE. The concept of disease and its implications for psychiatry. Br J Psychiatry. 1975 Oct;127:305-15. doi: 10.1192/bjp.127.4.305. PMID: 1182384.

5:  Breu AC, Axon RN. Acute Treatment of Hypertensive Urgency. J Hosp Med. 2018 Dec 1;13(12):860-862. doi: 10.12788/jhm.3086. Epub 2018 Oct 31. PMID: 30379139.

6:  Rossi GP, Rossitto G, Maifredini C, Barchitta A, Bettella A, Latella R, Ruzza L, Sabini B, Seccia TM. Management of hypertensive emergencies: a practical approach. Blood Press. 2021 May 8:1-12. doi: 10.1080/08037051.2021.1917983. Epub ahead of print. PMID: 33966560.

 

Graphics Credit:

The image at the top of this blog is for Shutterstock per their standard licensing agreement. I picked it based on the fact that it reminded me of a patient I saw in the emergency department when I was an intern.  He had a large left basal ganglia cerebral hemorrhage that was most likely due to sustained hypertension.

Apologies:

Editing this post was tough. For some reason my Word processer switched to Polish language and stopped automatically checking my grammar and spelling. That was compounded by the fact that I was dictating in Dragon and sound alike words that were spelled correctly were substituted.  I ended up proofing everything on my phone and just finished tonight (4/29).   

The Denial of Plasticity

For the past couple of months, I have spent a lot of my free time working on a presentation on neurobiology.  The presentation is the lead off in a series of lectures on addiction and the target audience is primary care physicians.  I have a lot of experience with this topic because I give a very similar lecture at least six times a year to physicians and other professionals who take a course on the treatment of addiction at the facility where I work.  I have been preparing and delivering these lectures for 3 1/2 years at this point.  Incorporating some of the most recent data on these topics is always a challenge and I depend a lot on Nature, Science, and Neuron for the latest reviews, research and commentaries.  In order to make it more relevant I ran across a collection of article in Frontiers in Psychiatry on the issue of whether or not addiction is a disease or not and it seems like a lot of that has to do with neurobiology.  Neurobiology has also become en vogue in many ways.  There is a conference posted in my clinic entitled "The Neurobiology of Play Therapy".  I thought I would post my observations of the implications of neurobiology in addiction and psychiatry.

The modern day interest in neurobiology owes a lot to Eric Kandel and his 1979 New England Journal of Medicine article "Psychotherapy and The Single Synapse."  The focus of that article was on the application of his basic science research on plasticity to the psychotherapy situation.  Plasticity was a relatively new concept at the time with the initial description of long-term potentiation (LTP) in 1973.  Kandel's basic argument was that nervous systems of varying complexity are designed to change with the experience of the organism.  The interesting part of his article is that it starts out with his experience as a psychiatric resident and the tension between the psychotherapists and the biological psychiatrists as they were called when I encountered the same dynamic in psychiatric training over twenty years later.  It is an important consideration because people outside of the field often have a skewed perspective of what makes up the training of a psychiatrist and this tension has been present for as long as I can remember - with articulate faculty on both sides.  He discusses this from the perspective of a parent discipline and an "antidiscipline" or one that is narrower in scope than the parent discipline and invigorates but does not displace it.  Neurobiology being the antidiscipline to psychiatry.  Molecular biology being the antidiscipline to cell biology and so on.  At the experimental level Kandel uses habituation and sensitization experiments on the sea snail to illustrate that "dramatic and enduring" changes in neural transmission occur with changes in plasticity.  He develops the theme that the functional-organic pathology based on gross or microscopic brain lesions is a false dichotomy.  Profound changes in networks of neurons can occur with no change in the numbers of neurons involved.  The mind is a function of the brain, but as Kandel later stated we do not have to think that all human behavior can be broken down to a specific biological level.

Getting back to the issue of addiction as a disease as opposed to something else offers a unique look at the plasticity concept and how it applies to brain problems.  I looked at all of the papers in the Frontiers series and briefly describe the details in the table below.  I would encourage reading the actual details in the papers since they are all freely accessible online and my one or two sentence summaries do not capture the complexity of some of these arguments. (click to enlarge)

There was a striking lack of the term "plasticity" in all of these papers.  It only surface in the paper on choice by Heyman in the following sentences: "First, most drug addicts quit.  Thus, drug induced plasticity does not prevent quitting."  That is a restricted view of plasticity.  First, it does not speak to the fact that plastic changes even if they appear to be long term can be reversed.  Second, it treats plasticity as a linear process when it is likely that the brain processes involved in recovery and in all of the other mechanisms cited by these authors as being more important in the recovery process are plasticity based.  The articles in general have the tone of polemics.  There is certainly nothing wrong with that.  As I have written on this blog, science is a dynamic process and part of that is an argument about theories over time.  The argument about the neurobiology of addiction seems to get hung up on both the disease concept and morality.  There can certainly be important neurobiology with or without disease.  That neurobiology is there whether or not medication, social processes, or psychotherapy influences it.  At least two of the authors equate neurobiological disease as the "no fault" condition and suggest that a biology based model is more blameless than one that suggests that addicts do have choices and respond to contingencies.  I think moral interpretations of a mental illness or addiction have less meaning if we are accurately describing the process.  It is much more than biology being no-fault and consciousness capable of decisions implying a moral judgment.  Plasticity mediated mechanisms gets us a lot closer to the science of how the brain works and away from the primitive interpretations of the 19th and 20th centuries.  

Plasticity is the best paradigm for describing addiction and the recovery process. Processes involving plasticity are all testable and the theory is falsifiable.  The most significant obstacle to the application of brain plasticity as a central process is the old functional-organic dichotomy where organic implied a neuroanatomical brain lesion.  It has been known from habituation and sensitization experiments like those described by Kandel in his 1979 paper that "dramatic and enduring" changes in neural transmission, do not require brain lesions or other abnormal anatomical features.  A recent paper (3) proposing that maladaptive NMDA-mediated synaptic plasticity as a unifying theory for tardive dyskinesia is a good example of plasticity mediated illness.  

There is no reason to believe that addiction and recovery may not be mediated by the same mechanisms.

George Dawson, MD, DFAPA


1: Kandel ER. Psychotherapy and the single synapse. The impact of psychiatric thought on neurobiologic research. N Engl J Med. 1979 Nov 8;301(19):1028-37. PubMed PMID: 40128.

" In each case, even in the most socially determined neurotic illness, the end result is biologic. Ultimately, all psychologic disturbances reflect specific alterations in neuronal and synaptic function. And insofar as psychotherapy works, it works by acting on brain functions, not on single synapses, but on synapses nevertheless. Clearly, a shift is needed from a neuropathology also based only on structure to one based on function."

2:  Alternate Models of Addiction.  Frontiers in Psychiatry.

3. Teo JT, Edwards MJ, Bhatia K. Tardive dyskinesia is caused by maladaptive synaptic plasticity: a hypothesis. Mov Disord. 2012 Sep 1;27(10):1205-15. doi: 10.1002/mds.25107. Epub 2012 Aug 1. Review. PubMed PMID: 22865512