Thursday, July 6, 2023

What are the odds that your blood pressure medication will really help you?



The answer might surprise you, not to mention a lot of people who have been labeled chronically ill.

Because that’s what it really amounts to:

Hypertension is a chronic disease, or rather a chronic condition.

When that label comes at an arbitrarily defined threshold of blood pressure then you are absolutely justified to seek an answer to this post’s title question. Particularly when economic interests are involved.

Such as the annual US$ 20 Billion market for anti-hypertensive medication.

That market virtually grew overnight when in 2017 the American College of Cardiology and the American Heart Association lowered the threshold for hypertension from 140/90 to 130/80 mmHg.

31 million Americans “became” chronically diseased “overnight”. The prevalence of hypertension among adults aged 40 and over jumped from 37% to close to 60% [1].

 Here is why I don’t agree with this threshold-fixing.

The True Risk Of Elevated Blood Pressure

Lowering elevated blood pressure, whatever “elevated” means, should reduce cardiovascular death (mortality) and disease (morbidity).

Only it doesn’t, a least not in the way it is portrayed to the public.

The gospel coming from, among others, the Framingham study tells us that there is a continuous increase of death risk as a function of blood pressure. With no detectable lower bound down to systolic pressure of 115 mmHg.

Courtesy of a study by Port et al. [2], the graph below shows how this statement is typically presented as a result of a statistical method that we call a logistic regression.

 

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What this picture does not tell you is that the choice of statistic (logistic regression) produces a smoothed line over the raw data.

 That’s a problem when those raw data look like this:

 

No alt text provided for this image


 

It is easy to see that the smooth line of the first graph does not describe the reality very well.

Cardiovascular and non-cardiovascular deaths show no significant upwards trend until about 160 mmHg. From then on the risk increases exponentially.

In such a situation a splined logistic regression is the more appropriate statistic model to use. That’s the type that accounts for a segmentally different relation between death and blood pressure.

When applying the more appropriate statistic there is no more significant association between death and “hypertension” up to the age-adjusted 70th percentile of blood pressure.

You are probably less interested in the finer points of statistics, than you are interested in a tool to help you answer the question: what is that 70th percentile for my age and gender.

 Calculate Your Personal Risk

You can calculate your age-adjusted 70th percentile of systolic blood pressure using the following formula:

  • For men: 120 + (2/3 x age); example for a 50-year old man: 120 +(2/3 x 50) = 153 mmHg
  • For women: 114 + (5/6 x age); example for 50-year old woman: 114 +(5/6 x 50) = 156 mmHg

You can find the Port paper from the bibliography below and even download it from the journal Lancet, one of the most respected medical journals.

 I bet, when you compare your 70th percentile threshold with your actual blood pressure your worries, if you have any, may become a lot more moderate.

 OK, so much about death, but what about cardiovascular disease? You don’t want to get that either.

The answer is surprisingly similar.

The Numbers Needed to Treat and to Harm

A very recent study looked at the number needed to treat (NNT) and the number needed to harm (NNH) in the context of blood pressure medication [3].

The NNT describes how many people need to take a drug to prevent one single event (in our context: heart attack, stroke etc.) compared to not taking the drug.

The NNH tells you how many people will need to take the drug to observe one harmful event or side effect.

Ideally the NNT is as small as possible, and the NNH as large as possible.  

In our case, no benefit of taking BP lowering medication was observable (over 3.5 years of monitoring) for people with a systolic blood pressure  (SBP) <140 mmHg.

At a SBP between 140 mmHg and 159 mmHg, the NNT was 47 and the NNH was 39. That is, 47 people need to be treated to prevent 1 major adverse cardiovascular event (MACE), whereas the remaining 46 would have experienced no event, even if they didn’t take the drug.  

And for every 39 drug-treated individuals there is one harmful event or side effect.

It has always escaped me why those who should inform the lay public about the benefits and harms of what they prescribe, shy away from these very illustrative numbers.

An earlier meta-analysis of studies which investigated the outcomes in treated vs. untreated hypertension (140-160 mmHg systolic & 90-100 mmHg diastolic) concluded that there was no benefit from treatment for heart disease, stroke or total cardiovascular events.

Oh, yes, and almost 10% of treated patients discontinued treatment, because of negative side-effects.

Mind you, this meta-analysis was performed by evidence-based medicine’s non-profit white knight, the Cochrane Collaboration [4].

Hypertension: Not To Be Taken Lightly

The latest iteration of the European Society Of Hypertension (ESH) guideline for managing arterial hypertension  reflects this cumulative evidence. It sets the “red line” for drug treatment at 140/90 mmHg.

But it also makes one thing very clear:

Elevated blood pressure is a warning not to be taken lightly. For 9 out of 10 hypertensive persons, their condition is self-inflicted. Too much weight, too little exercise and a lot of other unhealthy habits are the dominant causes of hypertension.

Which also means, correcting these causes may very well drive your blood pressure down, too.

That’s why all the guidelines agree on lifestyle change as the first line of defense against the potentially debilitating consequences of long-standing hypertension.

So, if you succeed in managing your blood pressure through lifestyle adjustments, you wouldn’t need to worry about the odds of your drugs helping, or harming, you in the first place.


Hashtags

#hypertension

#hypertensionawareness

#NNT

 

References

[1]     Kaul S. Evidence for the Universal Blood Pressure Goal of <130/80 mm Hg Is Strong: Controversies in Hypertension - Con Side of the Argument. Hypertension 2020;76:1391–9. doi:10.1161/HYPERTENSIONAHA.120.14648.

[2]     Port S, Demer L, Jennrich R, Walter D, Garfinkel A. Systolic blood pressure and mortality. Lancet 2000;355:175–80. doi:10.1016/S0140-6736(99)07051-8.

[3]     Mao Y, Ge S, Qi S, Tian QB. Benefits and risks of antihypertensive medication in adults with different systolic blood pressure: A meta-analysis from the perspective of the number needed to treat. Front Cardiovasc Med 2022;9:1–12. doi:10.3389/fcvm.2022.986502.

[4]     Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev 2012;8:CD006742. doi:10.1002/14651858.CD006742.pub2.

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Friday, April 5, 2019

How do you keep your cardiovascular system healthy from your fifties onwards?

Through robustification!

By making your cardiovascular system robust against aging.
Systems biology defines robustness as “… a property that allows a system to maintain its functions against internal and external perturbations.” [1]
When that “system” is your cardiovascular one, and the “perturbation” is aging then cardiovascular robustness is your ability to maintain cardiovascular function.
Measuring the latter gives you a benchmark to guide you to finding the strategies that work for YOU.
That’s important because not everything does. I’ll get back to that in a minute.
The other nice thing about robustification function is that it is your best bet at maintaining health AND living a little longer in good health.
Just look up the medical definitions of aging and chronic cardiovascular disease. Both share “progressive loss of function” as their key criterion.
So, why haven’t you heard before about robustness in the context of cardiovascular health? Because most medical practitioners and the majority of biomedical scientists haven’t taken note either.
Which is what all systems biologists find rather amusing. And which is why I have made it my vocation to change that (the “taking note” part, not the amusement). 
If you really want to read the heavier stuff on this you’ll find it for example in the Journal of Applied Physiology or others [2,3].
The CV system is unique in that it is the only system of the human organism that connects each and every cell. After all, the CV system’s chief task is to supply every cell of every tissue in every organ with the nutrients, the oxygen and the signaling molecules they need.
To accomplish that, Mother Nature has designed this system as a closed hydraulic system:
Its center piece is a pulsating pump (the heart) that pushes blood through a network of elastic tubes (the arteries).
Keep in mind that it is not the pump that does most of the pushing but the arteries. They expand to receive the heart’s output, and then recoil to push this “bolus” of blood further downstream.
This ability to expand and to recoil, together with the arteries’ ability to change their geometry, is what determines CV function.
In fact, what typically deteriorates first is not the heart. It’s the arteries.
With aging, arteries become stiffer. They progressively lose their elasticity (the correct term is ‘compliance’ but elasticity is easier to visualize), which puts more and more strain on the heart, until that strain becomes intolerable.
Long story short: the physical parameters that define arterial function (predominantly compliance and resistance) are the ones that tell you how slowly or fast you age.
Keep those functional parameters in the green zone, and you will have made your CV system robust against aging.
The only problem: you can’t measure them, yet.
My team and I have developed tools to do just that.
We use a common medical blood pressure measurement technique, such as the ones you know from your doctor’s office, or that you may even use at home to measure your blood pressure.
Until this technology becomes available to everyone, you can only go by what you have right now.
And what you have is blood pressure.
Blood pressure is determined by all those functional markers that I mentioned earlier.
Stiffer arteries means higher pressure.
Greater resistance to flow (for example when arteries are narrowed) means higher pressure.
Now I come back to the point I made earlier: what works for YOU.
Only if you monitor your CV function will you have a guide to what works for you and what doesn’t. Absent any method to monitor function, your second best bet is blood pressure monitoring.
Not every type of exercise, not every dietary or other strategy works the same in any two people.
Here is an example.
Green et. al. investigated the change of CV function (measured as flow mediated dilation, FMD, an indicator for arterial compliance) in 800 individuals following an 8-weeks exercise intervention. The result was a 7% increase in FMD on average. For that marker ‘FMD’ 7% is impressive [4].
Now look at the graph below, which breaks down the result for every one of the participants:
Each vertical bar in this graph represents the change in function of one participant.
Hardly anyone had a 7% change. In fact, the range goes from getting worse to improving by almost 15%.
Now you understand why you shouldn’t go blindly with the recommendations doled out by people who simply parrot what has been published in scientific research.
Aside from the dangers of getting mislead by the pseudo-scientific prattling of food fundamentalists, hardcore exercisers and people in general who present more aspirational versions of themselves, there is an actual need to monitor the effects of whatever you do.
In answering a Quora question related to improving blood pressure I have compiled a little chart that tells you where your CV system’s functional markers should be.
Monitor them regularly and compare their development against anything you do to improve CV health. You will soon find out what works for you.
Now here comes my personal anecdotal evidence.
I am 62, my wife is 64.
We have exercised for the past 20 years almost every day.
For the past 5 years we have practiced intermittent fasting (last meal of the day is at latest 15:00 – 16:00, following day’s breakfast comes at 09:00 after 60-90 minutes exercise, including high-intensity cardio routines and strength training). Breakfast consists of a smoothie that I designed to specifically address arterial function.
Our CV function places us at a biological age of around 40. The same goes for blood biomarker profiles.
Additionally, my wife has preserved the looks and the figure of a much younger age, as you can see from the admittedly amateurish video clip I made a few days ago.
Will that work for you?
It will in all likelihood do you no harm and probably improve your CV robustness. But the most essential point is: monitor your intervention’s effect on the markers of CV function. Even if you have only blood pressure to go by.
And if you are successful, you might even inspire others to pose that same question of yours already at a younger age. Because CV function begins to decline in mid-twenties already.
The earlier you start, the better.
Good luck.

Bibliography
1. Kitano H. Towards a theory of biological robustness. Mol Syst Biol 2007;3:137.
2. Kraushaar LE, Dressel A. The cardiovascular robustness hypothesis: Unmasking young adults’ hidden risk for premature cardiovascular death. Med Hypotheses 2018;
3. Kraushaar LE, Dressel A, Massmann A. A novel principled method for the measurement of vascular robustness uncovers hidden risk for premature CVD death. J Appl Physiol 2018;japplphysiol.00016.2018.
4. Green DJ, Eijsvogels T, Bouts YM, Maiorana AJ, Naylor LH, Scholten RR, Spaanderman MEA, Pugh CJA, Sprung VS, Schreuder THA, Jones H, Cable T, Hopman MT, Thijjssen DH. Exercise Training and Artery Function in Humans: Non-Response and Its Relationship to Cardiovascular Risk Factors. J Appl Physiol 2014;
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Tuesday, March 19, 2019

Weight Loss Aside, What Health Benefits From Intermittent Fasting?


I have been asked this question often enough to address it here.

Whether, and to which extent intermittent fasting (IF) transforms human health still needs to be seen, but there are some indications for beneficial effects.

IF refers to dietary patterns in which individuals (a) have no or very little energy intake for extended periods of time (e.g. 16–48 h), while having normal energy intake between these periods, and (b) follow this interval pattern on a recurring basis.

Naturally it is much easier to test the effects of such dietary patterns in shorter lived animals than in humans. Mice, with an average lifespan of 3 years, can give us much faster insight into intervention effects on health and life expectancy.

Some of the more promising effects of IF in animal models is improved glucose handling (relevant for preventing diabetes), and in aging related diseases such cardiovascular disease, Alzheimer’s dementia, and frailty.

One of the key pathways through which IF seems to work is cellular senescence, the aging of cells, that ultimately leads to functional decline and death. The fasting promotes an upregulation of the cellular repair mechanisms that are essential for keeping cells functional and preventing cell cycle arrest.

There is still a lot to be investigated because outcomes vary by animal model, IF protocol, age at which IF is introduced, and duration of the intervention. The same will probably hold true for humans.

Taken together, what we can safely say is that IF doesn’t harm you, in all likelihood improves glucose handling and potentially has some protective effects against cellular aging.

To which extent these effects prevent disease events (such as heart attacks, stroke, dementia) remains to be seen. We simply have insufficient data to claim either way.

The problem is that trials capable of showing such effects need to be of durations that are longer than what human participants willingly endure.

That’s why IF became a surrogate, and more tolerable, protocol for caloric restriction (CR) in the first place. CR refers to continuous restriction of energy intake to 30-50% below normal, while ensuring adequate nutrient supply.

This protocol has produced substantial expansion of life expectancy in primitive organisms, such as C. elegans (a microscopic round worm whose life is measured in days rather than in years).
But the higher up you go on the complexity ladder of species, the lower the returns. Still, in primates, our closest relatives, significant beneficial effects on health and life expectancy have been documented.

Unless you are really prepared to adopt a CR or IF lifestyle for good, my guess is that you may experience some subjective effects on health, but they will dissipate rather quickly, once you return to “normal”.

Let me give you a personal example. My wife and I have made IF a regular affair. Last meal of the day is latest at 16:00, first meal of the following day comes at sometime between 09:00 and 11:00, and always after 60-90 minutes pre-breakfast moderate-to-high intensity workouts.

Let’s call this a n=2 experiment/trial.
It gives us a 17-19 hours food-free period. Deduct from this 4 hours for the post-prandial period (the period of nutrient absorption following the day’s last meal) and we have a net fasting period of 13-15 hours.

We have been doing this for approximately 5 years now.
With my research focus on healthy aging and cardiovascular functionomics, I have, of course, designed this “trial” in accordance with best evidence, and I have the advantage of being able to monitor physiological functions for the 2 of us regularly, using a medical device that I specifically developed (together with my team) for this purpose.

Cutting a long story short: at 64 my wife has the cardiovascular function and fitness of a 35-years old woman, the body contour many 40-year olds wouldn’t mind to have (Just put a few seconds of, admittedly amateurish, video clips together, to prove my point).
At 2 years younger than her, I am not that lucky, but still can compete in the age range of men 20 years younger than I.

I attribute this to the summation of physical exercise, IF and dietary quality. In science speak, this is, however, only anecdotal evidence.

So, if you want to find out for yourself, go with the Nike motto:
Just Do It.


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