229 ‒ Understanding cardiovascular disease risk, cholesterol, and apoB

KEYPOINTS

• 01

  This is a compilation on why ASCVD prevention must start early.

  Attia assembles clips from earlier conversations, chiefly with Allan Sniderman and Tom Dayspring, with commentary in between, ordered as a primer on atherosclerotic cardiovascular disease, cholesterol and apoB. His premise: people under 30, 40 or even 50 think heart disease isn't their problem yet, and the data say otherwise.

• 02

  The first event is often the last.

  Historically, more than half of first heart attacks were fatal, which is why a cardiologist friend once joked he saw fewer heart attacks than pathologists. Survival has improved, but sudden death remains a common first symptom, so waiting for symptoms is a poor strategy.

• 03

  Events cluster earlier than people assume.

  In the data Attia shows, slightly over 50% of men who will have a cardiac event have it before 65, and almost 25% before 54. For women it's about one-third before 65; women carry the same disease burden but experience it about a decade later.

• 04

  Atherosclerosis starts in youth.

  Autopsy work by Herbert Stary and colleagues, and studies of young soldiers and accident victims, showed atherosclerosis in people in their 20s and 30s. The disease gets a foothold over the first three decades, and lesions that can cause clinical events typically develop from the fourth decade onward.

• 05

  The 10-year risk model has two fatal flaws.

  Sniderman credits 10-year risk calculators with a big step forward in the 1980s–90s, but under the 2019 ACC/AHA algorithms almost everyone is 'low risk' at 40, so treatment effectively starts at 55–60. First, because there are many more people under 60, the absolute number of events in 'low-risk' younger people is high even though the rate is low. Second, by 60 the disease has been progressing for decades.

• 06

  A population risk number isn't your risk.

  A 4.1% 10-year estimate means about 4 of 100 similar people will have an event, but real risk within that group varies widely. Telling someone their risk is above 7.5% also implies 92.5% of the time nothing happens, a weak motivator. Sniderman prefers lifetime or 30-year risk: for a 30-year-old, the risk to 65 might be around 30%, a number people can act on, and you can show how much benefit is lost by starting at 45 or 55 rather than 35.

• 07

  There's no 'good' or 'bad' cholesterol, only lipoproteins.

  Dayspring stresses that cholesterol is carried in lipoproteins, and the apoB-100 family (LDL, VLDL, IDL and Lp(a)) is atherogenic; apoB-48 on chylomicrons is set aside. Each atherogenic particle carries one apoB, so apoB counts the particles that enter the artery wall, in the presence of an injured endothelium.

• 08

  Standard lipid panels mislead.

  An LDL-C of 140 mg/dL says little about particle number. Standard panels give several numbers, but treatment decisions are mostly based on LDL-C, so the others 'do nothing'. Attia is pessimistic that medical training will switch to apoB soon, even though the 2019 guidelines leaned toward it.

• 09

  Mendelian randomization makes apoB the causal metric.

  Because genes are randomly allocated at conception, Mendelian randomization avoids much of the confounding that plagues 30-year observational studies. Studies in the last decade show apoB (and cholesterol) is causal while HDL is not, and that apoB outperforms LDL-C for risk.

• 10

  Lower apoB further and earlier.

  Sniderman suggests at least a 50% reduction in higher-risk people. Attia argues physiologic levels are below about 50 mg/dL; PCSK9 inhibitors routinely reach 20–40. Halving plasma cholesterol barely changes total body cholesterol, so very low levels aren't dangerous, and children live safely around 40. Attia thinks apoB of 20–30 from your 20s could largely eliminate ASCVD and treats an apoB of 60 (about the 5th percentile) as a ceiling.