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Archive for the ‘Hypertension’ Category

Some physics: Why is blood under pressure? 

In perfect vascular climatic conditions, the human circulatory system is comparable to a smooth flowing river irrigating 100 trillion cells, traversing many kilometers of the capillary network, to the far away tissue bed. One major difference in the river analogy is, that in human biology, the entire blood has to return back to the heart in about 30 seconds. (The fact that the venous system does this in style with near-zero pressure head is the greatest wonder in circulatory physiology)

The force per unit area, that drives the blood is the blood pressure. It is expressed in kilo pascals. (16/10 Kpa one Kpa is 7.5 mmHg. It has two components streaming pressure as well the lateral pressure. What we measure by conventional BP apparatus is the lateral pressure on the vessel, which is what we are worried about most times. But, the forward driving head is equally important because the branch points bear the brunt of this pressure head. Sudden surges and spikes attack the grade separators more. This is one of the reasons, the arterial branch points are more prone to atherosclerosis. Though we believe onward pressure head does all the damage, it is also worth knowing the velocity of blood flow can also be defining factor in vascular Injury. The flow velocity is surprisingly low in physiological conditions, about 4-6km/h something similar to our walking speed. 

What is normal blood pressure?

We don’t know. The search is going on. But, what is important is the net lifetime BP harming effect on blood vessels. Of course, BP is not a mono player, it interacts with other risk factors like lipids, diabetes, and smoking, along with genetic susceptibility, and epigenetic vulnerability, making cardiovascular events perfectly polygenic.  

How do we define and grade systemic HT?

A dozen different societies keep defining this (ACC/AHA. ESC, ISH, British, whatever be the normal,  one set of numbers is permanently etched in our mind ie 120/80 as the cut-off. 

A more philosophical definition would be, that high BP is defined as the BP at which our blood vessels feel the stress and strain and begin to wear out. We may never ever know that in a given patient. Now, we are adding more twists to this already confusing normality data. Namely nocturnal BP.

Why 24 hr /Nocturnal BP important?

If the average human lived for 75 years, he or she will be spending  25 years in sleep. What does our circulatory system do in those 25 years? We don’t know. We believe if the brain sleeps the vascular tree takes rest as well. How can it be?  The reticular activating system should go off mode, still the vasomotor centers should be vigilant enough to keep vital organ perfusion. Ironically, sleep can be stressful for some. During recumbent posture the fluid compartment redistributes and ECF expands especially in patients with renal and cardiac compromise. (Recall the mechanism of PND) .Add on to this, the ever-fluctuating sympathetic tone with REM/NREM sleep phases. One of the offshoots of widespread use of ambulatory BP monitoring is (ABPM)is the new term nocturnal hypertension. 

Defintion of nocturnal HT

The definition of nocturnal hypertension is, night-time BP ≥120/70 mm Hg (Now it is more stringently defined as >110/65 mm Hg by the 2017ACC/AHA guidelines. I am not sure, but I think this is applicable to anyone with or without HT irrespective of treatment.

Two more entities exist to confuse us. Just don’t bother. (Fellows can’t escape from this though). A Clinic and morning home BP of <130/80 mm Hg is defined either as masked nocturnal hypertension or masked uncontrolled nocturnal hypertension if they are already on drugs.

Night time BP patterns

Normally we expect 10 -20% dip in BP is expected.

The following are four nocturnal BP patterns defined:

  1. Dipper: 10-20 %;
  2. Extreme dipper, more than 20%;  
  3. Non-dipper: less than 10%, 
  4. Riser: 0%.or + side  (I think, this is the same as the reverse dipper )

 

An Important resource from HOPE Asia net work on ABPM Kazuomi Kario Journal of clinical hypertension.https://doi.org/10.1111/jch.13652 While everything looks ok, that blue line amuses us the most. These guys are also called reverse dippers.

Nocturnal dipping: Is it systolic, diastolic, both or mean?

Most studies documented as systolic dippers. Dipping is expected to Impact both systolic and diastolic BP similarly. But, we know it need not be. systolic BP is more volume-dependent, while diastolic BP is resistance is related. I think the concept of diastolic vs systolic non-dipper is yet to be evaluated.

How to measure? How many readings? 

  • Ambulatory BP monitoring equipment is the key. Few companies have defined and have patented software (Omran HEM series is the leader, Micro life is another one )
  • The night-time BP is calculated as the average of night-time BPs (from going to bed to arising) measured by ABPM The number of night-times BP measurements required may be ≥6.
  • The methodology is getting standardized. Errors in measurement are considerable. Posture, temperature, and inflation triggered awakening all matters. 
  • Substantial technology is still evolving. Remote wireless monitoring is possible (Apple and Google are keenly watching the global BP market potential !)

Management issues

Though there are 4 subsets in nocturnal BP patterns,  currently, Identifying non-dippers is the key target that will help diagnose more resistant HT. 

How to convert non-dippers into dippers?

  • Night-time dose of antihypertensive drugs to be encouraged.
  • Salt restriction in the evening diet 

How to prevent excessive dipper (>20%)

The reverse of the above advice is true in this subset. 

Isolated nocturnal  hypertension

I think it is an overzealous concept in sleep medicine. Let us wait and observe. Stojanovic, M., Deljanin-Ilic, M., Ilic, S. et al. Isolated nocturnal hypertension: an unsolved problem—when to start treatment and how low should we go?. J Hum Hypertens 34, 739–740 (2020).

Is there a J curve phenomenon  among dippers ?

We cant generalize,  pro-dipping forces are good & non-dipping forces are bad. Should we consider labeling excessive dippers as nocturnal hypotension? Considering the fact both non-dippers and excessive dippers carry more CVD risk. Like any other biological variables with dynamic safety margins, we are clueless about what is ideal dipping .(A nocturnal J curve)

Clinical trials on nocturnal hypertension 

  • JHOP study Kario K, Hoshide S, J Clin Hypertens 2015 from Japan is a very popular one on this topic.
  • While this elegantly done Finish study  (J.Hypertension 2004 ) stressed the importance of home BP monitoring. 

What is new in nocturnal HT management?

Melatonin, administered as circadian hormone therapy is expected to play a useful role as a night watchman in BP control (Frank et al Hypertension 2004)

Final message

Nocturnal hypertension is trying to emerge as a new cardiovascular risk factor. Understanding this condition and intervening seems to be important, considering the well-known fact, that cardiovascular events are clustered in the early morning hours.

Still, routine ABPM to know the status of nighttime BP in all hypertensive individuals is not warranted. However, people who had an event or who have secondary hypertension may need to do so. The simple truth is if you have a peaceful day and a perfect sleep, your BP is bound to dip naturally. So, the message to all those active and energetic men and women who are carrying a tag of hypertension need not worry about this dipping and non-dipping stuff. Instead, maintain a healthy lifestyle. There is a thin line separating awareness and anxiety.

Reference 

1.Yano, Y., Kario, K. Nocturnal blood pressure and cardiovascular disease: a review of recent advances. Hypertens Res 35, 695–701 (2012). https://doi.org/10.1038/hr.2012.26

2,Cuspidi, C, Sala, C, Tadic, M, et al. Clinical and prognostic significance of a reverse dipping pattern on ambulatory monitoring: An updated review. J Clin Hypertens. 2017; 19: 713– 721. https://doi.org/10.1111/jch.13023

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Next to the atmospheric pressure, the most curious pressure to understand is stored within the human circulatory system. Yes, it is the “blood pressure” fondly referred to as BP by both physicians and patients. (When worried men & women visit us and say, that they are suffering from BP, please make it a point to clarify, BP is a sign of existence of life, rather than a dreaded pathology ) 

Why should blood have pressure?

BP is lateral pressure exerted by flowing blood on the vessel wall (or is it the propelling pressure head ? It is to be noted, cuff pressure doesn’t measure this !) BP is generated by the heart in systole and sustained by the vascular system in both systole and diastole. BP is measured as mmHg. It can also be expressed as PSI(Pounds /sq Inch)  or Pascals or ATMs. If you allow me to spoil with some physics. Pressure is force per unit area ie Newton/m². So, pressure is essentially a force. Force is mass times the acceleration. Mass is weight independent of gravity, while the acceleration of blood is essentially the force of gravity added to the velocity of blood flow. If you think gravitational waves and planetary positions might influence the mass of blood (and hence the BP)  you may not be insane. (Environmental & astrological influence of BP and cardiovascular events need not a be mythology) (Oomman A,  J Indian Med Assoc. 2003 )     (Robert D Brook Cardiac clinic 2017)

How is it regulated?

Physics uttered at the bedside is sure to appear as nonsense for practicing physicians. Forget It. BP is not only a continuous variable, the neural, hormonal, cardiac control mechanisms are also in a dynamic flux. What we need to bother is, how to sustain a mean BP of around 90 mmHg within the human circulation, with robust autoregulation. (For the fellows in cardiology, it is a dangerously simplified teaching & belief  that cardiac stroke volume determines systolic BP and PVR determines diastolic BP) In fact, It is the systolic pressure that confers the energy required for diastolic BP. Regulation of BP is all about large vessel stiffness,  neuro-humoral tone of small vessels, water and sodium metabolism. This makes the kidney a central organ for long-term control of BP. It must also be emphasized BP is regulated in a regional and organ-specific manner. (Ex -The cuff brachial artery pressure may tell little about what is happening at the glomerular perfusion pressure )

Who are the guardians of BP?

Though general Physicians , Neurologists, Nephrologists even Endocrinologsts  have more geograhcial rights  cardiologists have largely taken siege over the entity of SHT because the heart happens to be a glamorous victim organ. We are witnessing an almost intoxicating number of cardiovascular trials on hypertension, right from Framingham’s days of 1970s to just released BP LLTC in 2021, trying to bring down cardiovascular risk. Based on the accrued evidence, the guardians of human  BP in various global institutions bring out strategies to reduce the risk of vascular injury. Have we succeeded in this  Intravascular number game.? I think we are. At what cost?

Two repeatedly asked two trivial questions 

  1. What is normal BP  &  When to start treatment?
  2. How much lower is best for our body?

Probably, we have got an answer for the first question from this Impactful publication. 

 

I think this study is trying to tell us, there is no normality for blood pressure in terms of risk reduction in cardiovascular disease. (Please recall, one JNC -Joint national committee  was dissolved after  including a controversial term pre-hypertension in healthy public  few years back) What will be the implication for this study? Its core conclusion is about 5 mmHg BP reduction across any subset of adult population will reduce CVD risk considerably. I am sure this study is so intense and powerful it will take at least a decade for its conclusion to fade away. So, can we make these funny conclusions? Hereafter we need not measure BP before starting treatment. Just administer drugs to any live adult who has blood & pressure. (J or U curve need a big debate later)

Mind you, sustained  5mmhg reduction* can be brought by any of the following habits. A salt moderated fruit-rich diet, reasonable physical activity, good sleep, a stroll in the park, yoga, a deep breath, having a pet, watching a movie in a quiet evening, having a loving  family, and so on so forth (Of course, 5mg Amlodipine, 40 mg of Telmisartan, or a  paradise device can do the same, with an add on pride)

*There is a big catch in this landmark paper. Read the title again. The important take-home point is that this 5mmhg lowering should strictly come by pharmacological means, not by any other means. (Correct me if I am not correct)

Final message 

We got the final answer from this marvelously done meta-analysis for the toughest question in cardiology. Hereafter  It’s going to be a celebration time for mankind, who struggle in a hypertensive world.

Post-ample

True, sustained high BP is a major risk factor for stroke, heart failure, and CVD. However, it is also true BP can’t* do much damage to the coronary artery without the help from its naughty cousins DM & dyslipidemia. All three parameters must be optimized in unison. May I propose a rough rule? It may be called DFL index for the collective CVD target.  Diastolic BP, fasting blood sugar and LDL all should converge around a unitless number of 70 to 80. 

*HT is a powerful risk factor for stroke and HFpEF. 

Reference

https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2900590-0

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We know LVH and SHT go together . Mind you , this is not an Intimate relationship.

Widespread utilisation  of echocardiography  has revealed  , definite  LVH occurs only in about 20% (A guess !) of  HT . (Do you know in the Famingham study the incidence of LVH  after 12 year follow up was a paltry 3 % .Will you agree with that ? Mind you , It was in 1969 when Echo was not there )

What determines LVH ?  The clear answer is elusive. It is easy to escape  from the issue by calling it  multi factorial !

Why don’t you try this question .

My guess would be ,  magnitude ( or  even duration of HT !)  is  less important than genetic predisposition  or  associated diabetes ,  renal involvement.Our analysis from  hypertension clinic reveals LVH is many fold common in secondary HT  when compared to primary HT !

I often used to provoke the students by saying if the LVH is gross in HT it can not be primary , 9/10 times  ! Invariably  we find some  other  association or reason for the HT !

Link to related topic in this site

Why-lvh-does-not-occur-in-all-patients-with-systemic-hypertension ?

How-diabetes-modifies-lvh-due-to-hypertension ?

incidence of lV left ventricular hypertrophy framingham study

Next  . . .

How does LVH regress with treatment ?

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Systemic hypertension (SHT )  is the commonest  clinical entity encountered in cardiology consultations . 95 % of  HT is considered primary. The remaining 5 %  form the most important class of HT (Secondary to renal parenchymal, vascular , endocrine,  etc)

How  intelligent is this traditional classification of HT  ?

The incidence of primary and secondary  HT varies depending  upon the level of investigation we do . One of my  regular patient  who gets to me for  HT .He  is 42 year old man  works in financial institution  with lots of work stress and he was marginally obese as well .  He was investigated for all known cause of secondary HT and every parameter  was found to be normal and was being treated as   primary HT.

When he was about to leave my clinic he  bowled  this google !

Doctor , why do  you call  mine as  primary HT   ?  . . . When you yourself  say  my stress and weight is responsible for  high blood pressure ?

Primary vs secondary HT

Valid question is it not !  . .  . I told him   “somehow”  ,   we have not  been taught   in medical schools  , to consider stress  of life  as a factor  responsible for  developing secondary  HT !

Final message

Strange  definitions in medicine continue .  Not every one with high stress  levels develop HT  .There  are  some unknown factors operating  .Till we know that we  will keep calling them as primary HT .

( Who  knows the  man  who raised this question  may   show up  with adrenal hyperplasia  or a renal parenchymal dysfunction 5  years down the lane !)

We live by perceived  knowledge  on a moment to moment basis  ! . Ignorance  tries  to lock the doors of knowledge .

But we  continue to open new doors . That is the  only  purpose of medical research !

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Left ventricular  hypertrophy (LVH) is one of the most common  structural heart disease.Systemic hypertension, aortic valve disease are responsible for the bulk of the cases .Some  of the LVH occur due to cardiomyopathy (HCM/Non HCM variants).Athlete’s heart is a physiological response to exercise and  it  is largely a normal entity.

How many patients with SHT develop LVH ?

It is surprising to note , not every patient with SHT develop LVH .In fact estimates suggest only  about 30-40% of chronic  hypertensive individuals develop SHT .

What are the determinants of LVH in SHT ?

  • Magnitude of systolic pressure
  • Magnitude of diastolic pressure
  • Pulse pressure
  • Duration of SHT
  • Age
  • Gender
  • Body  weight/Obesity
  • Effect of treatment

While any of the above factors may operate in determining LVH

none of the above are important than this

“Genetic susceptibility ”

The myosin isoforms are determined by the genes .The re expression of   fetal isoforms in adults is responsible for LVH in many .This is determined by the genetic homogeneity

LVH  in  renal disease

Secondary hypertension due to renal dysfunction is a major determinant of LVH. This is espcially true if the pateints are dialysis dependent.The mechanism are not clear .

Diabetes and SHT :  LVH  friendly forces

When diabetes alone and SHT alone is less likely to result in LVH the combination of these two entities greatly increase the likely hood of LVH.DM induced microangitis amplifies the after load effect of HT and result in early LVH.Further this LVH is different from pure forms of hypertensive LVH  in that the interstitium goes for hypertrophy and in some cases neovascualrisation. In hypertensive LVH it is predominately myocyte hypertrophy  with little interstitial  proliferation. this has important therapeutic implication as any drug which reduce the blood pressure can regress pure myocytic hypertrophy, while in diabetic LVH  regression is difficult to achieve .

Lipid levels inversely related to LVH ?

There is no consistent relation between lipids and LVH .Occasional reports suggest a negative correlation.

Which LVH is associated with diastolic dysfunction ?

It is a well known fact , LVH has major effect on LV diastolic function.But it is also a fact only some forms of LVH develop this. Now it is clear only if the interstitial hypertrophy occur  diastolic dysfunction is manifested.  Even as the as the hypertrophied  myocyte  continue to  relax  the interstitium do not have molecular mechanisms to relax .Hence, as discussed earlier , diabetic hypertensive patient often  develop diastolic dysfunction .

Final message

LVH is not a simple expression of raised after load.It has major  non hemodynamic determinants which if identified , could have important therapeutic implication.

Coming soon . . .

Can  coronary artery  disease induce LVH in the absence of SHT or DM ?

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