October 31, 2022

Cardiovascular Disease

#229 ‒ Understanding cardiovascular disease risk, cholesterol, and apoB

Not everybody dies from atherosclerosis, but… everybody dies with it."  —Peter Attia

Read Time 27 minutes

In this special episode of The Drive, we have pulled together a variety of clips from previous podcasts about cardiovascular disease to help listeners understand this topic more deeply, as well as to identify previous episodes which may be of interest. In this episode, Peter highlights the importance of understanding cardiovascular disease and why early intervention is critical. He also provides a primer on lipoproteins and explains the fallacy of the terms “good cholesterol” and “bad cholesterol.” Allan Sniderman discusses the metrics measured in routine blood work – along with the limitations of those standard panels – before explaining why apoB is a superior metric for determining risk. Additionally, Tom Dayspring explains the causal role of apoB in atherosclerotic cardiovascular disease (ASCVD) and the therapeutic goals for apoB concentration, and Peter explains how early and aggressive lowering of apoB could change the landscape of cardiovascular disease prevention.

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We discuss:

  • The importance of understanding atherosclerosis early in life [2:25];
  • Defining ASCVD, its causes, and the role of cholesterol [8:00];
  • Why early prevention of atherosclerosis is critical [13:45];
  • Preventing atherosclerosis—two fatal flaws with the “10-Year Risk” approach [16:00];
  • Intro to lipids and lipoproteins: why there is no “bad” or “good” cholesterol [23:00];
  • Limitations of standard blood panels [35:45]; 
  • How Mendelian randomization is bolstering the case for apoB as the superior metric for risk prediction [39:30];
  • Therapeutic goals for apoB concentration [58:15];
  • How early and aggressive lowering of apoB could change the course of ASCVD [1:10:45]; and
  • More.

§

The importance of understanding atherosclerosis early in life [2:25]

From episode #203 – AMA #34: What Causes Heart Disease?; discussed from [2:20] – [8:00] 

Atherosclerotic cardiovascular disease (ASCVD) is ubiquitous

  • 1 – This disease is inevitable and ubiquitous
  • 2 – It has a major impact on human longevity

Not everybody dies from atherosclerosis, but… everybody dies with it”‒ Peter Attia

  • Cancer and dementia are both prevalent with aging, but they are not inevitable
  • We know a lot about ASCVD 
  • Peter adds, “The reason you really want to understand this is because the impact is huge and the tools we have are also huge” 

Extending lifespan comes down to delaying the onset of chronic disease, and atherosclerosis is the most common chronic disease 

2 main paths to atherosclerosis (risk factors) 

  • 1 – Hypertension (high blood pressure) 
  • 2 – Lipid abnormalities (we’ll focus on this one)
  • Smoking is a behavioral risk factor (we’ll put this aside for the moment)

Studies of pathology show ASCVD begins at a young age 

What is the most common presentation for a 1st heart attack? 

  • Sudden death
  • A 1st heart attack in over 50% of people is fatal
    • Today this number is a little less but still staggering

What is the age distribution of people who have their 1st major adverse cardiac event? 

  • Adverse cardiac events are a heart attack or a stroke (or death)
  • Figure 1 shows the incidence of cardiovascular events for both males and females in the US

Figure 1. Incidence pf cardiovascular events by age and sex.  Image credit: JAMA Cardiology 2016

  • The graph on the right shows total annual events
    • The 1st 2 sets of bars show the number of events for people under 65
    • Men are shown in the darker bars comprising slightly below 25% and slightly above 25% of all cardiac events
      • The implication is that 50% of men who are going to have a cardiac event in their life will have it before the age of 65 
    • For women, a third of women will have their 1st cardiac event before the age of 65 
  • The total annual events is not the whole story; it’s important to understand how long it takes for this disease to take hold
    • Early prevention is key
  • Almost 25% of these events are in men younger than 54
  • When you think of someone who is 45, 50, this disease didn’t start 2 years before

When you see these stats laid out, it creates a shift in your mind around why you should care about this 

 

Defining ASCVD, its causes, and the role of cholesterol [8:00]

From episode #203 – AMA #34: What Causes Heart Disease?; discussed from [9:00] – [15:00] 

Atherosclerotic cardiovascular disease (ASCVD) is disease state characterized by the deposition or the buildup of cholesterol (sterols) in the artery wall 

  • It begins with a fatty streak that later consolidates into plaques that can ultimately lead to a reduction in blood flow
  • Reduction in blood flow is called ischemia 
  • Ischemia results in tissue damage to the heart and this is what results in a heart attack 
  • A heart attack can be fatal depending on the amount of cardiac tissue that is damaged from loss of oxygenation

Causes of ASCVD 

{end of show notes preview}

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  1. Enjoyed this very much. I still would like to know what Lipidologists think about *extremely* low ApoB and LDL-C on Repatha. How about a patient on Repatha, Zetia, and low dose Rosuvastatin (10) who now has a residual plasma LDL-C of only 4 mg/dl? Do you stop the Zetia and/or Rosuva to get this patient’s LDL-C in the range of 10-20 mg/dl? Seems like a simple question for which I have no answer…

    • This show does an excellent job of explaining ASCVD, apoB, and why early intervention is critical. Aside from that, it doesnt actually tell you what that intervention might look like. He beings the show by saying the tools we have to fight ASCVD are huge, but never actually tells us what those tools are. Are medications, specifically statins, one of those tools? Maybe just simple diet and exercise. This episode is like a good movie with a terrible ending.

      That said, I will be renewing my membership for the 3rd year, thanks for the hard work guys!

      • I have the same question as Andrew Lenz (“diet contributes little to cholesterol levels”) Thanks!

  2. Help! I’ve been looking for the figure/graph showing the % increase in incidence or CVD events (or maybe risk?) on the Y axis and mg/dL apoB on the X axis. I know Dr. Attia cites the 60 mg/dL level as a “ceiling” often, and I want to provide the figure (and the citation) to my doctor. I believe it was derived from the Framingham Heart Study, but I could not find it on that website. I also think I saw it in the show notes, but I cannot for the life of me find it anywhere. Thanks!!

  3. More than once, Dr. Attia has mentioned something along the lines that very little of the blood serum concentration of cholesterol (I think its something south of 10 or 15%) is attributable to diet, and the rest is manufactured w/in the body (presumably a result of lifestyle and genetics). The take home for some people may be eat all the bacon and brisket you want, day in and day out, and don’t worry about the effect on your cholesterol levels. Is this the correct take home? Or is a more nuanced version, that on any given day, the % from diet may be low, but a diet with sustained high levels of animal fat, or other saturated fats/cholesterol will increase your levels (and apoB, in particular) over time? I’d love to hear discussion of that when the “diet contributes little to cholesterol levels” factoid is used. Love the website and podcasts! I’m sure I’m already living a more healthy lifestyle because of them!

    • I had the same question. I would love to hear Dr. Attia’s answer to this question and maybe some in depth discussion with other Subject Mater Experts on the practical best management practices that we normal humans should be incorporating in our daily life.

  4. My understanding is that there is huge longstanding evidence that dietary fat intake does not positively correlate to ASCVD incidence. More solid correlation exists for dietary Carbohydrate, especially sugar intake and ASCVD. If this is so, what is the relationship between chronic Carbohydrate intake and ApoB particle levels — in other words does the endothelial damaging effect of Carbohydrate overload and Hyperinsulinemia work at any level through ApoB particle effect?

  5. Although I generally prefer new info over these recaps (which penalize regular listeners a bit), this one was really good. But it still left one big practical question unanswered, as did the epic 5-part series with Dr. Dayspring:

    If a doctor won’t prescribe a PCSK9i without first trying a statin, but is happy to let the patient decide on the choice of statins, how would you decide which statin to start with?

    Which statin would you start a patient on, assuming a hypothetical example where ApoB is ~100, age is 50, and the patient is extremely fit with about 100 met hours per week of exercise?

  6. Does taking statins make sense if Apo-B level is mid-range but LDL-C is somewhat elevated?

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