brandonb

This study was really interesting to me since it showed that very low cholesterol levels--the average LDL was 43 mg/dL in the study--don't just slow the buildup of coronary plaque, but actually reverse it. About 4 in 5 patients in the study saw plaque volume go down, as measured by CCTA.

Every article I've seen about Galleri mentions false positives as the main objection.

So I ran the numbers. For adults age >50 (the recommended group), standard cancer screening generates 33 false positives per cancer case detected. Standard screening + Galleri detects 236% more cancers with just 8% more false-positives for this age group.

The numbers would be slightly worse for a younger cohort, but still better than I'd have thought.

Lp(a) is stable since it's mostly genetically determined.

ApoB is very responsive to diet and medication--you can lower it by about 85%.

A few reasons:

- If you made a dietary change (e.g., more fiber and less saturated fat), the tests tell you whether it actually worked.

- Statins are dosed based on the LDL or ApoB reduction you need. The most powerful statins cut cholesterol by 50%, but at higher doses the risk of side effects does go up.

- Other medications like PCSK9 inhibitors and ezetimibe exist, and whether to use them depends on the other numbers. For example, PCSK9 inhibitors have a secondary benefit of lowering Lipoprotein(a), and statins and GLP-1s have a secondary benefit of lowering inflammation.

- If blood pressure, HbA1c, etc is high, then there's a slightly different set of diet advice and a very different set of medications. For example, lowering blood pressure through diet is mostly about reducing sodium and increasing potassium.

Coronary CT calcium scans are getting more popular. But before getting one, I'd do these simpler tests first:

- ApoB - about 20% of people with normal cholesterol results will have abnormal ApoB, and be at risk of heart disease.

- Lp(a) - the strongest hereditary risk factor for heart disease.

- hs-CRP - inflammation roughly doubles your risk of heart disease

- HbA1c - insulin resistance is a risk factor for just about everything.

- eGFR - estimates the volume of liquid your kidneys can filter, and is an input to the latest heart disease risk models (PREVENT).

These are simple blood tests. You can get them for <$200 through my company or others: https://empirical.health/product/comprehensive-health-panel

Imaging is great for detecting calcified plaque in your coronary arteries. But before you have calcified plaque, the above risk factors tell you about the buildup of soft plaque. And 4 out of 5 of them are modifiable through lifestyle, exercise, and medication.

Very fair caveat!

IMO, one of the most interesting things about the new hematology guidelines is that they're likely to get people treatment for symptoms like fatigue or low energy. A lot of doctors consider these "vague" complaints that are hard to diagnose. For some fraction of those cases, low ferritin or iron might be low hanging fruit.

Yep, LDL cholesterol is one of six biomarkers:

* ApoB or LDL cholesterol

* Blood pressure

* Inflammation (hs-CRP)

* Lipoprotein(a) (strongest hereditary risk factor)

* HbA1c (metabolic health)

* eGFR (kidneys)

Modern cardiovascular risk calculators like PREVENT take all of biomarkers factors and give you a 30-year forecast of your risk of heart disease.

Typo—thanks for pointing it out, I fixed the post.

The 55 mg/dL target in this study is somewhere between the 1st and 5th percentile.

70 mg/dL (the control) is around the 10th percentile.

IMO, surprising that reductions at the low end still seem to yield such large benefits. I'd expect it to saturate much earlier.