March 20, 2023

Cardiovascular Disease

#247 ‒ Preventing cardiovascular disease: the latest in diagnostic imaging, blood pressure, metabolic health, and more | Ethan Weiss, M.D.

If everybody got truly optimal medical therapy, if we didn't have barriers to using all these tools in everybody, I think this disease would largely be controlled.” —Ethan Weiss

Read Time 54 minutes

Ethan Weiss is a preventative cardiologist at UCSF, an entrepreneur-in-residence at Third Rock Ventures, where he is working on a project related to cardiometabolic disease, and a previous guest on The Drive. In this episode, Ethan compares and contrasts the diagnostic imaging tools, CAC (coronary artery calcium score) and CTA (CT angiography), used to image plaque—including the latest in CTA software—and how these tools inform our understanding of ASCVD risk and guide clinical decision-making. Ethan discusses the types of plaque that cause events and the data that make a case for optimal medical therapy over stenting outside of particular cases. He explains why high blood pressure is problematic and walks through the data from clinical trials testing aggressive treatment. He talks about the best way to actually measure blood pressure, why we shouldn’t simply accept that blood pressure rises with age, and how he uses different pharmaceutical agents to treat hypertension. Additionally, Ethan explains our current, but limited, understanding of the role of metabolic health in ASCVD. He discusses the impact of fat storage capacity and the location of fat storage and explains how and why there is still a residual risk, even in people who have seemingly normal lipids, don’t smoke, and have normal blood pressure. 


We discuss:

  • Ethan’s entrepreneurial work in the cardiometabolic disease space [4:30];
  • Calcium scans (CAC scores) and CT angiography (CTA), and how it informs us about ASCVD risk [6:00];
  • Peter’s historical CAC scores, CTA results, and how one can be misled [10:45];
  • How Peter’s CTA results prompted him to lower his apoB [14:45];
  • Calcium scans vs. CT angiogram (CTA) [21:15];
  • How Ethan makes clinical decisions based on CTA results and plaque burden, and the importance of starting treatment early to prevent ASCVD [28:15];
  • Improved methods of CTA to grade plaque lesions and how it’s shaped medical decisions such as stenting [33:45];
  • Why Ethan favors optimal medical therapy over stenting outside of particular situations [41:45];
  • The need for FFR CTA, and the potential for medical therapy to eliminate ASCVD [54:00];
  • The fat attenuation index (FAI) and other ways to measure inflammation in a plaque [57:30];
  • Statins and exercise may increase the risk of calcification, but what does this mean for risk? [59:45];
  • The root cause of statin hesitation despite evidence that statins are a profoundly important intervention [1:05:30];
  • Importance of keeping blood pressure in check, defining what’s normal, and whether we should just accept higher blood pressure with age [1:10:45];
  • Blood pressure variability, how to best measure it, and data suggesting the enormous impact of keeping blood pressure down [1:21:00];
  • Drugs for treating high blood pressure recommended by the ALLHAT trial [1:35:15];
  • What the SPRINT trial says about the aggressive treatment of hypertension, and the risks of such treatment [1:38:15];
  • Confirmatory results in the STEP trial for blood pressure, and how Ethan uses the various pharmacological agents to lower blood pressure in patients [1:43:15];
  • The role metabolic health in ASCVD: what we do and don’t know [1:51:00];
  • The impact of fat storage capacity and the location of fat storage on metabolic health and coronary artery disease [1:56:15]; and
  • More.


Ethan’s entrepreneurial work in the cardiometabolic disease space [4:30]

Ethan’s career has evolved over the past couple of years 

  • Ethan had a bit of a midlife crisis and decided he didn’t want to keep doing the same thing for the next 25 years
  • He was given the opportunity to get involved with a local group of investors who create biotech companies 
  • He closed his lab and has become a volunteer clinical faculty at UCSF 
    • He sees patients infrequently 
    • He spends most of his time working to build a new company (he’ll explain more later)


Calcium scans (CAC scores) and CT angiography (CTA), and how it informs us about ASCVD risk [6:00]

A quick recap of what a calcium score (CAC) is and a CT angiogram (CTA) 

  • They spent a lot of time talking about the distinction between calcium scanning (CAC) and CT angiography (CTA) in Ethan’s previous podcast (at 1:40:15)
  • They used the analogy that a calcium scan demonstrates a sight of a prior injury
  • What we know is that the more calcium you have in your arteries, the worse you do 
    • The higher the risk of both cardiovascular and all cause problems
    • We suspect that calcium represents a healed plaque, so the amount of calcium you have in your arteries is strongly related to the amount of plaque that you have in your arteries

We know that the amount of plaque you have in your arteries is related to your risk of having heart attacks and dying from heart attacks 

  • Ethan uses an analogy with his patients‒ a calcium scan is like a satellite image of your heart
    • It gives you a sense of any damage that has occurred over your lifetime
    • It also gives you a nice adjunct indicator of your overall risk of dying from a heart attack
  • One of the nice things about a calcium score is it’s very, very low in radiation
    • Even CTAs are low now (we’ll talk about that later) 
  • The calcium scan is also a very inexpensive tool; some places do these scans for ~$200
    • (But you can still find some places still charging $2,000+ for the same scan)
  • The calcium scan is a low-risk procedure; it doesn’t require dye
  • And it provides great insight, especially the first time it’s done 

Ethan did a “full 180” on the utility of calcium scans 

  • When he first started his cardiology practice in the early 2000s, he thought calcium scans were annoying, and he didn’t know what to do with them 
  • Obviously there’s epidemiologic value in understanding the risk of different populations
  • Now he finds value in many contexts and even in individual patients
  • A calcium scan doesn’t have value for everybody; in a 25-year-old, it is probably not worth anything
  • Calcium scanning is now a tool that he uses regularly
  • Peter explains this to patients as a 2×2 of young versus old and zero versus non-zero calcification (see the figure below) 
    • There are two areas where the scan provides insight (shown in blue below)
      • Older people (70+) who have zero calcification
      • Young people (45 or 50) who already have calcification
    • And there are two areas where the scan does not provide insight (shown in white below)
      • If a 40-year-old has a calcium scan of zero, you haven’t really learned a lot
      • Further, if a calcium scan of zero in a 40-year-old is accompanied by other risk factors, Peter would not be dissuaded from aggressively treating those risk factors
    • Similarly, when an 80-year-old has a calcium scan of zero, you might be less inclined to push for aggressive measures
      • Even though there could be false negatives

Figure 1. 2×2 for interpreting calcium scan results, with informative results highlighted in blue.

  • Peter has spent some time in the literature on this and learned that a calcium scan is a relatively imprecise measure
    • The thickness of the slices that are used in that scan are significantly greater than the slices that are used in the CT angiography


Peter’s historical CAC scores, CTA results, and how one can be misled [10:45]

  • When Peter was in his mid 30s (2008/2009), he had his first calcium scan
    • At the time, his doctor thought he was crazy because he was 35 and exercising at least 24 hours a week

{end of show notes preview}

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Ethan Weiss, M.D.

Ethan Weiss got his bachelor’s degree from Vassar College. He completed his MD and residency at John Hopkins. He then went to UCSF where he completed a clinical fellowship in cardiology and postdoctoral research training. Dr. Weiss is an Associate Professor in the School of Medicine at UCSF where he practices preventive cardiology and conducts research.

In his research, Dr. Weiss uses genetic models to better understand the mechanism of metabolic disorders such as obesity, fatty liver disease, and diabetes. He also studies the blood clotting system and has interest in identifying novel ways to safely block clots associated with diseases such as heart attack and stroke without causing an increase in bleeding. He has conducted randomized clinical trials to assess the impact of nutritional interventions on weight loss, insulin sensitivity, and metabolism. 

Currently, Dr. Weiss has shifted his attention to entrepreneurial work at Third Rock Ventures.  He is working on a project related to cardiometabolic disease. He is also the Co-Founder and Medical Advisor for Keyto, a company that created an app and program to make it easier to follow a Mediterranean-style keto lifestyle. [UCSF Profiles]

Twitter: @ethanjweiss

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.
  1. Peter / Ethan:

    Thank you for this conversation.
    * 44 year old man, south asian heritage, but raised almost exclusively in the US.
    * 6 – 12 months ago, CAC 218 (76.9 LAD, 3.18 LCX, 138 RCA).
    * Immediately started statins, cholesterol down to 138 from 10-yr avg of 220.
    * Direct LDL down to 76.
    * ApoB first measurement ever at 62
    * Excited to investigate PKCS9 inhibitor
    * BP using at home Withings 3x avg over 2 – 3 months ~125 / 80

    My questions for you given my 99th percentile CAC for age
    1) how can I find a cardiologist to start working with that is at the front edge of the science like both of you?
    2) value in longitudinally monitoring CAC?
    3) value in augmenting with CTA (or variant)?

    I am planning to immediately look into PKCS-9

  2. Hello Peter and Ethan,
    This is a very timely and relevant podcast for me, personally. I am an active 66 year-old man. I exercise 4-5 days per week (1+ hours per workout – cardio and weights). I have a family history of high blood pressure and high cholesterol. My father managed his cholesterol but suffered a major stroke at the age of 88 and died at the age of 94. My mother (96) has had several minor strokes but is still living and shows only partial loss of memory and cognition.

    I have had elevated cholesterol (Total: ~240, LDL: ~140) and blood pressure (135/90) for the last two years. My PCP recommended a CAC test. I had the test performed at the beginning of 2023. Out of pocket cost – $150
    The results were startling: Total Calcium Score: 2000
    – Left main: 0, LAD: 718, Circumflex: 669, RCA: 613
    Needless to say, I was very concerned. I went to see a cardiologist for the very first time in my life. I should note that I have never had any chest pain or tightness in my chest that would have suggested a problem. In late January I started on a daily 10mg dose of Crestor (statin) and baby aspirin.

    I had an echo stress test a week ago, a lipid panel and APO B/A1 ratio blood test a day ago. The stress test showed no significant blockage or abnormal heart function. My lipid panel and APO A1/B results are very encouraging.
    APO B/A1 Ratio: 0.3
    – APO A1: 185 mg/dL (down from 192 in 2015)
    – APO B: 55 mg/dL (down from 96 in 2015)
    Total Cholesterol: 156 mg/dL (down from 243 in October, 2022)
    Triglycerides: 64 mg/dL (down from 76 in October, 2022)
    HDL Cholesterol: 91 mg/dL (up from 86 in October, 2022)
    VLDL: 13 mg/dL (no change)
    LDL: 52 mg/dL (down from 144 in October, 2022)
    Total Chol/HDL Ratio: 1.7 (down from 2.8 in October, 2022)
    non-HDL Cholesterol: 65 mg/dL (down from 157 in October, 2022)
    My exercise routine has remained the same. I also continue to consume (and enjoy) a glass of red wine with dinner every evening. My daily diet continues to include salads and vegetables, daily.

    So, what has changed?
    1) daily dose of 10mg Crestor and one baby aspirin
    2) a major change in diet with regard to “high cholesterol” foods
    – 90% reduction in: dairy products (e.g., cheese, butter, ice cream), processed foods, chips, eggs, red meat, poultry, cookies and other bakery items
    – 100% elimination of pork
    My resting blood pressure is now 116/76 (down from 135/90). My resting pulse is 48 (no change). My weight is 159 lbs (down from 164 lbs in October, 2022).

    I strongly believe my change in diet has had the most significant impact on my cholesterol levels. One takeaway from my own experience is that eating healthful foods does not negate the ills of eating harmful foods.

    All this being said, I would not have been as disciplined about my change in diet had I not had the hard data of the Coronary Artery Calcium Score (CAC Score). The results of this test back in January hit me like a brick. I had heart disease and needed to do what was necessary to manage and mitigate the risk of a stroke and/or heart attack. The CAC score is such an easy, quick and low cost test. It is very unfortunate that more people do not take this test. Indeed, most people do not even know about this test and its significance.

    Thank you very much for your very interesting and informative podcasts regarding important topics including cardiovascular disease and the actions we can take (medically and through lifestyle changes) to prevent and reduce our risks. For those of us who want to live long lives in good health and good spirits the information you share with us is invaluable. With”heartfelt” appreciation, Bob

  3. There’s a current thinking that the keto diet works as well. This would include red meat and pork as well as high fat cheeses. Most of the diet preferably will come from fats (70 percent). While I agree with eating vegetables I see vegetables as carbohydrates. It’s also the dressings on your salad that could contain sugars and carbohydrates. I am currently
    torn about staying on my statins after recently been diagnosed with high cholesterol. I will have to say goodbye to my love of fruits especially before bedtime as well as fruit juice. The cookies and cakes have been gone since my recent diagnosis as well. . I found a beef protein powder that seems to help get me through the day. I’ve added some exercise and I’m hoping for better numbers next go around.

  4. Genetics and individual metabolism have much to do with how changes in diet will impact our cholesterol and associated particles in our bodies. Changes that reduce cholesterol in one person may not be as effective for another person making the same adjustments in diet. With regard to the keto diet, I think a diet that promotes products from hoofed animals (dairy, red meat, pork, …) over healthful vegetables such as beets and sweet potatoes is not optimum for our long-term health including reducing the risk of heart disease. Admittedly, this is just one perspective based on my experience and my metabolic “lens.”

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