Cardiovascular disease is a solved problem

There are multiple independent risk factors for heart disease. The major ones are:

  - LDL / ApoB
  - Blood pressure
  - inflammation (hs-CRP)
  - Insulin resistance (HbA1c)
  - Lp(a): strongest hereditary risk factor.
  - eGFR: a measure of kidney function

Non-statin drugs like PCSK9 inhibitors have been shown to reduce heart attacks, strokes, and other cardiovascular events on top of statin therapy. One randomized control trial was FOURIER in 2017: https://www.nejm.org/doi/full/10.1056/NEJMoa1615664

Why do we see consistent dose response between LDL lowering SNPs and cardiovascular disease in Mendelian randomisation studies, then?

> [that circulating LDL is the cause of heart disease] is false.

I think your comment really owes the rest of us more explanation of this part.

*statins?

Simplifying, we are all essentially born with heart disease. It's just a game of how long it takes for it to kill us. No way around it.

Unfortunately, our biology isn't perfect.

The article goes on to say it's not all LDL. Keep reading. The first part agrees with my cardiologist, at any rate

> High LDL is correlated with the development of heart disease, but it does not cause heart disease.

You realize this sentence is an oxymoron?

Unless you meant to say "it does not cause the development of heart disease". I agree correlation is not causation.

I think there's a a bit of a paradox here: cardiovascular disease is solved biomedically, yet still remains the #1 cause of death worldwide.

From a biomedical standpoint, we have highly accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, knowledge of nutritional biochemstry, and next generation drugs like PCSK9 inhibitors and lepodisiran that can lower ApoB and Lp(a) by 90%. So there's no fundamental reason why cardiovascular disease has to be in even the top 10 causes of death.

Practically speaking, providing guideline-recommended preventive care would require ~27 hours per doctor per day. And the incentives are misaligned: health systems profit when hospital beds are full, so they lack the business model to actually invest in prevention.

So it's a clear illustration of a systematic gap between research and care delivery.

“Solved problem” is too strong of language, but the cardiologists I follow are generally open about the idea that we have enough tools and knowledges to reasonably prevent and manage it the average person.

Even without medications, we’ve had enough knowledge about diet and lifestyle factors that the average person (excluding generic abnormalities that lead to abnormally high risk) could reasonably avoid heart disease through lifestyle and diet alone. That’s easier said than done for a lot of people in the modern world, so it’s good that we have a few different medications on top of that knowledge.

It's almost entirely a lifestyle problem. Shit diet, lack of exercise, obesity, &c. Overlap maps of obesity and cardiovascular deaths, they're virtually the same

https://ec.europa.eu/eurostat/documents/4187653/10321616/dea...

https://ec.europa.eu/eurostat/statistics-explained/images/th...

Ages ago, I used to do the typesetting for the _Cardiosource Review Journal_ (lived my life around the publishing schedule because no one else was able to run a WordBASIC macro to do initial formatting, import that into a page layout program, process all the graphics and place them, and generate page proofs early enough that it could be proofed and corrected with a 24hr. turn-around until a postal rate increase killed it) --- cardiologists seem very big on data/analysis, moreso than most other medical fields.

following a few cardiology conference i tend to agree with you, far from this sadly

Ask yourself what happens to them if it’s solved.

I mean their livelihood is predicated on it not being solved for a portion of the population

My cardiologist recently told me the disease is mostly from Lipo(a) and small dense Ldl, that it took decades from being able to measure LDL and note the correlation to disease to be able to measure there more specific factors, and even more time to nail down the observations.

Lipo(a) is genetic, apparently either you have it or not.

Small dense ldl is caused apparently (not a biologist) from high triglycerides, one cause of which is high sugar diet.

I think the title is deliberately provocative, but they're not wrong.

Heart disease is largely solvable from a biomedical standpoint: we have accurate biomarkers (e.g., ApoB, Lp(a), hs-CRP), long-term risk prediction models, precision nutrition, and highly effective next-generation drugs (PCSK9 inhibitors, lepodisiran, etc).

But practically speaking, heart disease remains the #1 cause of death due to bottlenecks in care delivery: e.g., 46% U.S. counties have no cardiologists, providing guideline-recommended preventive care would require ~27 hours per doctor per day, and incentives are misaligned (health systems profit when hospital beds are full, not from prevention).

I agree with you, but I suppose the point of the article is that we can solve cardiovascular disease without first solving obesity or chronic inactivity.

Obesity is solved! Tirzepatide.

GLP-1's baby.

I wish the “counter points” to my claims were always as bad as that link. It has a little bit of everything, from Fauci to seed oils to a Joe Rogan video.

Here is the chief editor of JAMA internal medicine arguing there is not enough evidence to prescribe statins for primary prevention in those 40+: https://www.natap.org/2016/HIV/ied160021.pdf

Your article starts by comparing the harms of statins to the harms of scary COVID vaccines. I'm not sure it's very credible.

Dramatic clickbait titles should expect to get responses that match.

Thanks for sharing this — amazing resource and resembles my experience with US health care.

I recently asked my doctor at Stanford - a pretty expensive hospital but one of the top cardio hospitals in the country - to get me an APoB test. He said that it may not be covered by insurance.

So instead I spend $360 or so on a year worth of biomarkers from Function Health that included ApoB and others

Lepodisiran has reduced Lp(a) by 94% in clinical trails. After it gets approved, IMO the author should re-write this section.

There are other cardiac failure modes too, for example electrical and hypertrophy.

The main side effects of statins are muscle pain and brain fog (from some statins -- others cross the blood-brain barrier much less).

The benefit of statins is to not only lower LDL cholesterol, but also inflammation, which is now actually a stronger risk factor for cardiovascular disease than cholesterol: https://www.empirical.health/blog/inflammation-and-heart-hea...

Layering PCSK9 inhibitors, ezetimibe, and statins can lower ApoB/LDL cholesterol by 85–90%, which would have been unheard of until recently.

On the horizon, drugs in clinical trials lower Lp(a) (the strongest hereditary risk factor for heart disease) by 94%. Currently, there are four RNA-based drugs in trials that effectively silence the gene that makes Lp(a) in liver cells: lepodisiran, olpasiran, pelacarsen, and zerlasiran.

I’m old enough that my parents/spouse’s parents are all on statins. They all report side-effects, mostly digestive issues.

I’ll eat a healthy diet, exercise, and live a life without persistent diarrhea. I’ll take statins if/when they are medically necessary, and no sooner.