Not All Heart Disease Risk Factors Are Created Equal.

Approximately 100 people in the US will die yearly from choking on a pen lid. Arguably, pen ownership could be considered a risk factor for early death1.

Not to minimise these pen-related deaths but let’s put things into perspective.

About 3.4 million people die each year in the United States. Pen-related deaths as a percentage then account for approximately 0.0029% of all deaths2.

How about something more dramatic?

Terrorism and homicide-related deaths.

In the US, terrorism and homicide make up about 58% of news coverage, so they must be a big deal in terms of yearly deaths?

Combined, terrorism and homicide deaths account for less than 1% of all deaths and homicide deaths account for most of them at 0.9% of these deaths.

Cardiovascular disease and cancer, however, make up about 65% of all deaths, yet they only account for 16% of US news coverage. Cardiovascular disease makes up only 2.5% of that 16% figure3.

Generally, there is a very poor relationship between what we see expressed in the media and what is causing the most deaths. Consequently, we often have very skewed perceptions of what impacts our risk of disease and death.

Let’s put things into perspective by looking at 45-year-olds tracked for over 20 years to see what factors increased their risk of cardiovascular disease the most4.

Having an early family history of cardiovascular disease increased the risk of having a major cardiovascular event by 50%. That’s a big deal and why people with an early family history of cardiovascular disease should pay particular attention to their cardiovascular risk.

However, having diabetes increased that same risk over 10-fold.

Not all risks are created equal. 

Diabetes was the risk factor associated with the highest risk of cardiovascular events. The second highest risk factor was metabolic syndrome, increasing the risk of a major cardiovascular event by sixfold.

As a reminder, metabolic syndrome is when you have 3 of the following 5 criteria.

  1. High blood pressure

  2. Low HDL cholesterol

  3. High triglycerides

  4. Abnormal blood glucose

  5. Enlarged waist circumference

I have covered this in a Tweet thread that I will link below.

As you can see from the graph above, high blood pressure, obesity and smoking all increase your risk of a cardiovascular event by 4 to 5 fold. But remember that having diabetes was double any of these individual risks.

In terms of risk, this is huge.

But what blood tests predicted the highest risk, as opposed to whether someone had a condition such as diabetes or high blood pressure?

Having a high number of LDL particles (Apolipoprotein) increased a person’s risk by about 90%. Again, a major deal.

However, cholesterol particles suggestive of insulin resistance (LP IR) increased that risk by over 6 times5. Having high cholesterol is dangerous but putting it in the context of insulin resistance is significantly worse.

Insulin resistance is a topic I will cover in later posts. In short, it drives metabolic syndrome and type 2 diabetes; hence, all 3 cluster together as the most significant risk factors.

These risk factors significantly increase a person’s risk of cardiovascular disease, but other factors are at play.

Depression increases the risk of a cardiovascular event by 4 to 5 fold. Premature menopause doubles a female's risk of a cardiovascular event6.

But risk factors rarely occur in isolation. The real danger is when they cluster together, as is most often the case in real life.

For those who are diabetic smokers with high blood pressure, their risk increases about 13-fold. If you add in high cholesterol, it shoots up to about a 42-fold difference.

But it gets worse.

If you add in doing no exercise, that risk now goes to an eye-popping 183-fold difference.

But wait, there’s more.

If you take all the above risk factors and add in obesity, that figure gets to a ‘bite the back of your hand’ 333-fold increase7.

Risk factors matter.

Risk factors, in combination, matter a whole lot more. 

Figure 2: Risk of acute myocardial infarction associated with exposure to multiple risk factors. Note the exponential Y axis.

The other element that matters is how prevalent a risk factor is. This doesn’t matter for individuals (You either have it or you don’t), but at a population level, it does.

Take smoking, for example.

Smoking is undoubtedly a huge risk factor in the development of cardiovascular disease. However, rates of smoking worldwide have decreased significantly. Consequently, although the risk of smoking to those who continue to do so remains the same, its impact on the population level changes. This is known as population-attributable risk (PAR) or the incidence of the disease due to an exposure, i.e. smoking.

While smoking worldwide still accounts for 44% of PAR in males and 15.8% of the PAR in females, high cholesterol accounts for 52.1% of the PAR in males and 53.8% of the PAR in females8. This is explained by the fact that although fewer females smoke, about the same amount have high cholesterol compared to males.

When thinking about cardiovascular risk, you cannot view each factor in isolation. Adding one risk on top of the other results in an exponential change rather than a linear one.

A simple analogy would be to think of speed and car crashes as the risk changes exponentially9. Driving 10 miles per hour over the speed limit increases your risk of a car crash.

Driving 20 miles per hour over the speed limit increases it even more, but not a little more; it doubles it. By the time you reach 50 miles per hour over the speed limit, your risk of crashing is shockingly high.

Yes, speed matters, but how much faster you are going has a disproportionate impact.

Ernest Hemingway wrote about bankruptcy happening in two ways.

“Slowly. Then suddenly “

Cardiovascular risk is the same.

One day you have one risk factor, and it increases your risk. Then you have two risk factors. But your overall risk has not changed slowly; it has changed suddenly.

Exponential risk is not something that humans intuitively understand.

Physiology, however, does not care about our poor understanding of exponential risk.

But you will.


 

Tweet Thread On Metabolic Syndrome

 

1

https://www.independent.co.uk/life-style/why-do-bic-pens-have-a-hole-in-their-lid-to-stop-choking-a6856061.html

2

https://www.cdc.gov/nchs/fastats/deaths.htm

3

https://ourworldindata.org/causes-of-death

4

Association of lipid, inflammatory, and metabolic biomarkers with age at onset for incident coronary heart disease in women. JAMA Cardiol 2021;6:437–47

5

Association of lipid, inflammatory, and metabolic biomarkers with age at onset for incident coronary heart disease in women. JAMA Cardiol 2021;6:437–47

6

Sex-Specific Risk Factors Associated With First Acute Myocardial Infarction in Young Adults. JAMA Netw Open. 2022;5(5):e229953.

7

INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52.

8

INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52.

9

https://www.emcins.com/losscontrol/insights-d/2020/08/speed-increases-risk/

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