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Tuesday, July 21, 2020

Thoughts about the epidemiology of exercise volume and health effects

Considerable data exist that  allow reasonable estimates of the volume of exercise required to 1) decrease cardiovascular disease (CVD) risk 2) decrease the risk of heart failure.

There are considerable coarse grain epidemiologic data that support the notion that regular aerobic exercise will decrease heart attack risk,reduce heart failure risk and reduce all-cause mortality.

The 2018 Physical activity guidleines for Americans recommended at a minimum of  approximately 8 metabolic-equivalent hours per week ( 8 met-hours or 500 met minutes per week.)

The recommendations translate to 150 minutes of moderate exercise (less than 7 Mets) or 75 minutes of vigorous  exercise per week.

 Arem et al ( 1) pooled data from 6 studies (661,137 men and women) and  demonstrated a 20% reduction in mortality among those who exercised at the recommended level with an HR of 0.8 (CI 0.78-0.82) and a 37% lower risk for those who exercised at 2-3 times the minimum level and the maximal benefit at 3-5 times the minimum (  0.61, CI 0.59-0,62)

Further no excess risk was evident even at exercise levels of 10 times the minimum.

Wen et al (2) published all cause mortality  data similar  to Arem and  also found that the maximum  CVD mortality risk reduction (45%) ( HR 0.55 CI 0.46-0.66)  at an exercise level of 523 minutes per week, a level roughly 3.5  times the minimum recommendation.

These 2 articles are part of the evidence  regarding the safety of exercise levels higher than the 2018 recommendation. Drs Carl Lavie and James O'keefe had earlier spoken ( TED) and warned  about the purported hazards of long bouts or too many years of aerobic exercise. In 2015,  perhaps in part reaction to the Arem article and commentary by Dr. Ben Levine,  Lavie and O'Keefe toned down their emphasis on the risk of long distant running.See here for a Runner's World article concerning that issue.

The conclusion to the Arem publication is refreshingly non-ambiguous and prescriptive ,quoting

"In regard to mortality health care professionals should encourage inactive adults to perform leisure time physical time activity and do not need to discourage adults who already participate in high-activity levels."

Coarse grain epidemiological evidence strongly support the generally accepted notion that people who exercise none or very little have the highest risk and those who exercise the most have the lowest risk.

In a nutshell the large coarse grain epidemiologic studies demonstrated that relativity low levels of exercise are better than none and further these studies were not able to demonstrate a upper level of exercise that is more risky than no exercise  though some data indicted that risk reduction at the highest level studied was perhaps slightly less protective than the next highest level .

It is possible that there could  be some harmful or potentially harmful cardiac effects in a small numbers of long time and/or high volume endurance athletes that would not be detected by large data analysis such as that of Arem and Wen.

 That appears to be the case.

There are  three  conditions that  appear to be more common in high level exercisers. These are 1) atrial fibrillation 2) myocardial fibrosis and 3)coronary calcification.

While the current consensus view is that the relationship between exercise level and all-cause and cardiovascular mortality is curvilinear and not U shaped, the same cannot be said in regard to atrial fibrillation (AF) .

In a  2018 review (4) of the "extreme exercise hypothesis", which is basically that there is some level of exercise achieved by some endurance athletes that results in a harmful effect. Three conditions have been considered in that regard: 1) atrial fibrillation (AF), 2)myocardial fibrosis (detected by MR gadolenium scaning) and 3) acceleration of coronary artery calcification (CAC).

Eijsvogels,Thompson and Franklin (4) concluded in regard to AF :

 "that the relationship between physical activity and incident AF is best summarized by a reverse J shaped curve.Light to moderate  amounts of exercise decrease but large volumes of exercise potentially increasing the risk of AF."

Two of the studies influencing their conclusion  are  the Henry Ford study and Anderson's cross country ski study .

Even though a study from the Henry Ford Exercise testing project (5) demonstrated that higher cardiorespiratory fitness was associated with a graded reduction in AF (the higher the fitness level the lower the risk of AF),a large cohort study of cross-country skiers showed that those who finished more races and those who raced faster had higher risk of AF than those who did only one race and those who raced at a slower pace. In that study by Anderson  (6) of  52,755 long distance skiers those who finished five or more races versus those who finished only one race had a Hazard ratio for AF  of 1.29 95% CI 1.04-1.61.

The Henry Ford study looked at the relationship between fitness and incident AF and the Anderson study looked at volume of exercise and intensity of exercise and while  fitness and exercise level are correlated they are not the same. After the entry into the study when fitness level was determined there is no data on  the exercise history of the participants at Henry Ford.The Anderson study used number of races and speed of racing to give some broad measure of amount exercise which relates to the questions of exercise volume versus AF risk which is not directly addressed by the Henry Ford study.

The large mega data studies,such as Arem and Wen have published, lack the statistical power to detect any mortality effect that might occur from AF,CAC and myocardial fibrosis in endurance athletes whose exercise volumes fall at the right end of the volume axis.

Even though the relationship between exercise volume and/or intensity and CVD and all cause mortality is not U shaped, the relationship between exercise volume and AF is.

1)  Arem H   et al. Leisure time activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Int Med 2015 Jun 175 (6) 959  (full text is on line)

2)Wen,CP Minimum amount of physical activity for reduced mortality and extended life expectancy .A prospective cohort study. Lancet 2011,378 , 144.

3)Franklin, BA Exercise related acute cardiovascular events and potentially deleterious adaptations
following long term exercise training. Placing the risks into perspective-An update A scientific statement from the American Heart Association. Circ 2020 Feb 26 PMID 32100573

4) Eijsvogels, TMH et al The "extreme exercise hypothesis":Recent findings and cardiovascular health implications." Curr Treat Opions cardio med 2018 20  84

5)Querishi,WT Cardiorespiratory fitness and risk of incident atrial fibrillation:results from the Henry Ford Exercise (FIT) project Circ 2015: 131 ;1827

6) Anderson K et al Risk of arrhythmias in 52, 755 long distance cross country skiers: a cohort study
 Eur Heart J 2013 Dec 34 (47)36

addendum 7/27/2020 Several changes made in the et to clarify meaning .

Thursday, June 18, 2020

If high levels of exercise increase risk of coronary calcification does it also increase CV mortality

Do long time endurance athletes have an increased risk of coronary calcification? If so, does that correspond to an increase risk of cardiovascular events?

In this study (1)  the life long exercisers in the highest activity level (5-6 hours of vigorous activity per week) did show an 11% increase coronary artery calcification (CAC) of a score of 100 or higher but that group had an all cause and cardiovascular mortality risk lower than that in groups with a lower level of exercise.

The author conclusions:

"This study suggests there is evidence that high levels of physical activity (3,000 MET-min/week)are n iassociated with prevalent  CAC but are not associated with increased all-cause 0r CVD mortality after a decade of follow-up, even in the  presence of clinically significant CAC levels."

To the extent these results reflect reality,there may be some reassurance to folks who may have spent arguably too many hours running or cycling.

1) Defina, LF et al. Association of all-cause and cardiovascular mortality with high levels of physical activity and concurrent coronary artery calcification. JAMA Cardiology, 2019 42 (2) P174 (full free text available)

" a man hears what he want to hear and disregards the rest" The Boxer,, Simon and Garfunkel

Tuesday, June 16, 2020

Gain in life expectancy related to exercise not a U shaped curve phenomenon

Moore et al published an analysis of the effect of leisure time activity and the effect on life expectancy with data from over 650,000 individuals with a 10 year followup in persons aged 40 and over.

At the lowest exercise level which was 3.74 met-hr/week ( a MET level of 3 is described by the authors as a brisk walk and this level being equivalent to 75 minutes of brisk walking per week) there was a gain of 1.8 years.

150-300 minutes of a brisk walk per week yielded 3.4 years gained.

300- 449 minutes of brisk walking was associated with 4.2 year increase in life expectancy.

The lowest level at which they demonstrated a life expectancy gain was less than the minimal recommendation of WHO and of the US panel. Benefit seemed to plateau at around 300 mintues of brisk walking per week. Moore's data display was not U shaped.

1) Moore, SC Leisure time physical activity of moderate to vigorous intensity and mortality. Plos Med 2012 e1001 335

2) Aengevaeren,VL Exercise and coronary atherosclerosis. Circulation vol 141 no 16, 21 april 2020 p 1338 1350

Nicholas Taleb schools public health specialists,libertarians and pseudo-libertarians

Nicholas Taleb addresses pubic health "thought leaders", non-devout libertarians and pseudo-libertarians in this commentary regarding the issue of recommending masks for the public.

Some of the points he made include:

1)A significant and vocal and authoritative portion of the public health coterie (PHC) mistook or ignored the important distinction between "absence of evidence of efficacy" and "proof of lack of efficacy".The PHC did not have anything in the second category in their argument tool box. They mistook or ignored the distinction between  absence of evidence and  evidence of absence,something emphasized in epidemiology 101.

2) The PHC failed to recognize how effective the widespread use of mask would be.If A and B both wear masks, both protect the other This Taleb labelled the compounding effect. Witness the hair care business in which 2 stylists were infected and none of the 140 patrons exposed developed covid19. The secret was both the stylists and all of the customers used masks.

3)Libertarians and pseudo-libertarians are admonished by Taleb to remember the primary principle of libertarianism which is the non-aggression axiom. Exposing fellow humans to a serious illness  with whom a person comes in contract just might be considered an act of aggression.

On 6/15/2020 Dr. Fauci admitted that masks were not recommended earlier because there was a serious shortage of masks. Interestingly once masks or face coverings were recommended by the PHC masks of all sorts were available all over the internet. What if the public had been told earlier  that cloth face coverings could help, would there have not been the release of entrepreneurial energy (and charitable efforts) to get masks to people that we see now. Wonder how many deaths could have been prevented. 

Friday, May 08, 2020

Exercise and the aging heart versus aging in the sedentary heart

What are the arc (s?) of the normal aging heart ( the sedentary ageing heart and the exercising ageing heart).Are they different?

 Humans seem good at finding patterns-sometimes even from patternless noise.One of the stories told  by physiologists and cardiologists regarding the age related downhill course of cardiac function seems to go  something like this.

One way to simplify  cardiac function is to consider the two parts of the cardiac cycle,1) contraction and ejection of blood and 2) relaxation and the refilling of the ventricle.

There are data indicating that the first signs of an impending problem are seen in the filling phase ie. diastole.From extensive echocardiographic and invasive physiologic measurements in humans the following sequence can be sketched out and penciled in.

First, there is impaired relaxation following by decreased elastic recoil and later diminished  compliance ( which is to say increased stiffness) and then -at least according to work from the IEEM group- remodeling of hearts with thicker walls and smaller ventricular volumes).Simply put- a sedentary ageing  lifestyle leads to a small stiff heart and long time endurance exercise leads to a larger more easily filled heart.The contractile function of the heart is well preserved with ageing , at least as indicated by measurement  of the resting ejection fraction.( increasing stroke volume with exercise is another matter as is left ventricular stress measured by speckle echo.)

This is largely consistent with the mainstream echocardiographic model which proposes a predictable,progressive process beginning with impaired relaxation,followed by decreased compliance and ultimately- as a compensation- elevated left side filling pressures.This model describes three phases of diastolic dysfunction indentifiable by combination of echo findings believed to reflect  how well or poorly blood flows into the ventricles from the atrium. This model recognizes that the various indices ( e.g E/A ratio, IVRT,maximal E wave velocity and the time constant of isovolumic pressure decay (Tau) change with age so that what would be abnormal in a 20 year old is normal in a 75 year old.It is thought that that filling pressure can be estimated by use of this model. NOTE-see end note 1 for reference to data that challenges the mainstream model by in part  providing data that cardiac cath measurements of left sided pressures do not regularly correspond with the three echo defined stages of diastolic dysfunction)

Next I consider  what I have labelled as the "Dallas or IEEM theory" of cardiac ageing.
I do not know if Dr. Ben Levine would approve of my label or not.  see end note 2

A series of articles from the University of Texas Southwestern Medical School and the IEEM have provided extensive invasive and noninvasive data regarding cardiac function at various ages and the effect of longtime endurance exercise versus sedentary ageing on  cardiac structure and function.

Levine et al first demonstrated that lifelong endurance athletes ( 25 years or more of running a lot) had left ventricular compliance virtually identical to those of sedentary 20-30 years olds. Then they compared ventricular compliance in four groups of 25 each of people who exercised at various levels over a 25 years period. These were all subjects over the age of 64 and were screened to excluded pre-existing heart disease.Group 1 was sedentary people who exercised no more than one session per week. Group 2 were labelled "causal exercisers" and exercised 2-3 times per week. Group 3 (Labelled as committed exercisers}worked out 4-5 times per week and the "competitive" group trained 6-7 times per week and regularly raced.The racers had the most elastic  or compliant ventricles while group 3 was "very close" in terms of ventricular compliance while groups 1 and 2 has significantly stiffer hearts.Note: while exercise seemed to help maintain compliance , long time endurance exercise did not mitigate the age related loss of ventricular relaxation-as measured by the isovolumic relaxation time  (ivrt) which is the time from aortic valve closure to mitral value opening.

Next, Levine studied a group of 70 year old subjects  and an vigorous  exercise program was unsuccessful in improving the reduced compliance observed in that group. Next another study demonstrated that middle age subjects with a year long exercise program ( that involved in part high intensity interval training) were able to increase their ventricular compliance.This implies that past some point in time you cannot improve LV compliance with endurance training  with some interval training but middle age may not be too late.This does definitely not mean that exercise for those 70 years of age and older gain no benefit from aerobic exercise,,just that it looks like they will not  improve left ventricular compliance (at least withinthe time frame of Levine's subjects)

In another article Levine said that exercise in the range of that performed by the "committed exerciser" might be adequate.

My main question in this regard is "how much exercise "is sufficient to maintain a healthy compliant left ventricle." Levine's amazingly compliant  (pun intended) subjects not only stuck with program for a full year but after the first 6 months participated in a hig intensity interval program using the demanding 4X4 workout program that involves 4 minutes of exercise at 95% of maximal heart rate followed by 4 minutes of rest done four times.

End note 1. Grant et al (Grant A, Grading diastolic function by echocardiography:hemodynamic validation of existing guidelines.Cardiovascular Ultrasound 2015 513 :28) compared echocardiography results with  left heart catherization data in 460 patients.The data demonstrated that there were no differences in regard to left ventricular pressures between patients with normal diastolic function and those with grade 1 or 2 diastolic dysfunction but there were differences between normal and grade 3 diastolic dysfunction in patients with reduced ejection fraction.In those patients with preserved EF, there is no statistical difference between normal and any grade of diastolic dysfunction. (see figure 5 of their article which graphically illustrates the lack of the "predictable, progressive process "which characterizes the  current paradigm.)If the detection of elevated LV pressures which generally correlates with exertional shortness of breath is in part the goal of echo studies of diastolic function it appears to not be reached based on Grant's data.

end note 2. Dr Ben Levine is the director of the Institute for Exercise and Enviromental Medicine (IEEM) housed at the Texas Health Presbyterian Hospital Dallas and professor at University of Medicine Southwestern. His group have done a series of comprehensive physiological studies on subjects recruited from the Dallas Heart Study, a population based sample of 6100 subjects in Dallas .

In a nut shell the concept is that everyone with aging develops some degree of diastolic dysfunction related to impaired relaxation and loss of diastolic suction,Later aging (particularly sedentary ageing) is associated with loss of ventricular compliance ( AKA increased stiffness). A long term endurance exercise program is capable of mitigating the changes in compliance but not the decrement in relaxation and diastolic suction. IEEM's studies  further indicate that a sedentary lifestyle may lead to a small stiff heart which may be the precursor to heart failure with preserved ejection fraction (HFpEF) ) and the Dallas group suggest that an appropriate amount of endurance type exercise begun no later than early middle age may play an important role in the prevention of HFpEF.

"Humans are pattern-seeking story -telling animals and we are quite adept at telling stories about patterns, whether they exist or not".Michael Shermer.

End note 3:In 2008, Shermer coined the term "patternicity" -the tendency to find meaningful patterns in meaningless noise. I am not suggesting that the extensive,very carefully done research referenced above is meaningless noise.I just really like the quote but I certainty hope the "Dallas hypothesis" ( my term) is a reasonably accurate approximation of the ways things  really are at least sometimes- having spent a lot of time running a lot over the last 40 plus  years.


Saturday, April 25, 2020

Has the issue of keep closed longer or open up quicker now a political non-debate?

The following is a quote from a commenter named Handle on Arnold Kling's blog from 4/25/20202 entitled Henderson-Wolfers Non-Debate.

"One of the most terrible things than can happen in our society is that some important and formerly neutral questions becomes politicized and the position one espouses become a strong signal of affiliation to a particular team....once there is a party line on the matter thinking ends all together."

Two  examples-Several members of the Republican party appear in Congress not wearing masks
presumably to make a point. ER Nurses stage a counter protest against a open things up protest,shouting matches break out.

Thursday, April 16, 2020

Should Runners,walkers,cyclists beware the Coronavirus slipstream

The slipstream is the zone behind a person moving (walking, running,etc) which pulls the air along with the person.In the racing world it is known as drafting.

A recent news article about a study done by Belgian engineers has gone a bit viral itself.The wave of air flowing carrying respiratory droplets or drops  in the wake of a runners goes behind him   for distances greater than the magic 6 feet that we are admonished to respect as regards proximity to other humans in the world or preventive social distancing. At least the animations released by the researchers give that impression as do their data which at this writing has not yet been published in a peer reviewed journal.

See here for details.

If their  animations reflect the actual path  of exhaled particles,one might decide that even when you are out for a run to wear a mask at least some of the time.

See here for some questions and answers from one of the authors of the paper.

My personal take home is that when a runner passes me I should move to the side to avoid potential particles in his slipstream and ( with an abundance of caution) pull my mask up until the passer is 20 to 30 thirty feet  away. In the increasingly unlikely instance in which I actually overtake a runner and pass her I should move to the side and keep to the side to keep the passed person out of my slipstream.

Perhaps the equivalent of "My mask protects you,your mask protects me" for runners could be
"I'll keep you out of my slipscreen,you keep me out of yours"

According to the authors data a cyclist should stay 60 feet directly behind the bike in front or keep off to the side. Also they suggest that 16 feet behind a walker and 32 feet behind a runner to be approximations of the "aerodynamically equivalent social distance" which is six feet for stationary people.


Sunday, March 29, 2020

Role of masks for COVID prevention outside of hosptial use

The following is my opnion and not a medical recommendation.

 Public face mask use appears to be common in Asian countries and also is now required in 
the Czeck Republic where people wear masks as a civil duty with the  shared realization that "I protect you by wearing a mask and you protect me by wearing a mask."

Corona virus is spread by droplets by infected persons even if they are asymptomatic and both simple surgical type face masks and the more expensive and protective N 95 masks can significantly reduce spread of coronavirus.

Both type of masks have been scarce in the US as Covid 19 cases exploded. Expectations and then realization of actual mask shortages in medical care facilities lead public health officials to discourage the public from using masks in the hope that more would be available for health care workers

Sometimes it has been argued that the masks were not effective when used by the public while at the same time saying that the masks should be reserved for medical personnel use in whose hands they would somehow offer important protection to them. Of course, protection is not a function of one's profession.

It is likely that it was believed that  officially recommending masks would lead to a large public demand  , making it even more difficult for health facilities to obtain masks.

As Covid  19 cases continue to increase and the mask shortage worsened, the CDC  said that masks can be reused and ,that homemade masks and scarfs could be used as a last resort by health care workers. This was a major change in CDC recommendations.Home made masks and scarfs can be used to protect the public as well, although that was not said by CDC.

Jeremy Howard,a Deep Learning specialist from Stanford, has posted an excellent review of the use and value of face masks by the general public to decrease COVID spread and describes widespread use by the public in many countries.See here

He gives links to sites with important information on how to clean masks and how to make masks at home from towels, t shirts etc. Some may worry about being accused of taking masks away from doctors and nurses if they wear a mask in public. Home made masks hopefully defuse  that issue.

Covid 19  is spread by droplets by asymptomatic as well as symptomatic persons
Various kinds of masks decrease risk of spread
Masks can be made at home and worn in public  without shame .A great DIY project
Masks  protect others perhaps even more than they protect the wearer
It has been suggested that it would be unpatriotic for the public to wear masks.I suggest the opposite.
wearing masks is patriotic.An asymptomatic covid 19  infected person being in public exposing others to the disease is certainly not patriotic.
I am not recommending  to bid up prices of masks,No one wants to take masks away from HCWs.
 But if you already have masks on hand ,wear them .If not they really can be made at home and will offer some important protection . Yes, less than the properly fitted and correctly worn N 95 and less than surgical masks but significant protection nevertheless.
Bottom line wear masks in crowds (including grocery shoping)

Finally, imagine for a moment if only 25% of subway riders in New York (8 million riders per day) wore masks for the last 2 -3 weeks what the results might have been. Also imagine the potential benefit after we all come out emerge from sheltering in place how potentially important wide spread use of mask might be in decreasing the risk and/or impact of a second wave.

The following quote is from Scott Alexander writing on his blog slatestarcodex.com on 3/23/20 giving a detailed analysis on the research of various masks and the protection they provide;

". So should you wear a mask?

Please don’t buy up masks while there is a shortage and healthcare workers don’t have enough.

If the shortage ends, and wearing a mask is cost-free, I agree with the guidelines from China, Hong Kong, and Japan – consider wearing a mask in high-risk situations like subways or crowded buildings. Wearing masks will not make you invincible, and if you risk compensate even a little it might do more harm than good. Realistically you should be avoiding high-risk situations like subways and crowded buildings as much as you possibly can. But if you have to go in them, yes, most likely a mask will help.

In low-risk situations, like being at home or taking a walk, I mean sure, a mask might make you 0.0001% (or whatever) less likely to get infected. If that’s worth it to you, consider the possibility that you might be freaking out a little too much about this whole pandemic thing. If it’s still worth it, go for it.

You are unlikely to be able to figure out how to use an N95 respirator correctly. I’m not saying it’s impossible, if you try really hard, but assume you’re going to fail unless you have some reason to think otherwise. The most likely outcome is that you have an overpriced surgical mask that might make you incorrectly risk-compensate.

If you are a surgeon performing surgery, bad news. It turns out surgical masks are not very useful for you (1, 2)! You should avoid buying them, since doing so may deplete the number available for people who want to wear them on the subway."
Here is a quote from a blog post by Tomas Pueyo entitled "Coronovirus:The Hammer and the Dance"which has attracted considerable interest.Here is the link.https://medium.com/@tomaspueyo/coronavirus-the-hammer-and-the-dance-be9337092b56

Pueyo considers masks part of the solution." (my bolding)
"the massive impact of policies like those of Singapore or South Korea:
  • If people are massively tested, they can be identified even before they have symptoms. Quarantined, they can’t spread anything.
  • If people are trained to identify their symptoms earlier, they reduce the number of days in blue, and hence their overall contagiousness
  • If people are isolated as soon as they have symptoms, the contagions from the orange phase disappear.
  • If people are educated about personal distance, mask-wearing, washing hands or disinfecting spaces, they spread less virus throughout the entire period."

(note the blue and orange wording references refer to charts in his article)

Maybe it is this simple: If asymptomatic patients are not contagious, the masks only for the symptomatic rule works, but if the  asymptomatic are contagious that rule does not work.

addendum: 4/11/20 Several glaring typos finally corrected. Also now the CDC has blessed the wearing of face masks by the general public, preferably of the home made variety.Two days ago at the grocery about 50% of the shoppers wore masks, most not of the DIY type.

Addendum 5/8/20 Today at Krogers only 2 of the approximately 40-50 person did not have masks.All of the store workers did and now they have erected plexiglass barriers shielding the checkers.