Thread by @nicknorwitz

Why Lp(a) May Not Be as Dangerous as You Think—If This One Metric Is Low (🔗 in 8/8)

1/8) A new study offers real hope for those with high Lp(a), a genetic risk for heart disease. While you can’t change your genes, the risk of high Lp(a) appears to be conditional on a modifiable factor: your waist-to-hip ratio.

2/8) For context, Lp(a) is a cardiovascular boogeyman. Unlike LDL, its unique apolipoprotein(a) tail makes it "sticky," more likely to promote blood clotting, and more atherogenic on a per-particle basis.

Your Lp(a) level is largely genetically determined, a fact that has been frustratingly difficult to address as few effective, proven therapies currently exist that lower Lp(a) and lower cardiovascular risk.

3/8) This new analysis used data from the landmark MESA study to understand this risk. It followed 4,652 people for a median of 17.4 years, tracking 'new cardiovascular disease-related events'—a composite including heart attack, fatal/nonfatal CHD, specific angina, stroke, and other atherosclerotic deaths.

4/8) The study's goal was to test whether waist-to-hip ratio—a proxy for visceral fat—modifies the risk from high Lp(a)? The finding was an unambiguous 'yes.’

The study states, "in individuals with a lower waist-to-hip ratio, Lp(a) levels were not significantly associated with increased cardiovascular risk".

Look at this graph: the orange line (high Lp(a), low WHR) shows a risk profile nearly identical to the blue line (low Lp(a), low WHR).

5/8) Digging deeper, researchers divided participants into three equally sized groups ('tertiles') based on their WHR, and the pattern was crystal clear. In the two-thirds of participants with the lowest and middle WHR, high Lp(a) conferred no statistically higher incidence of CV events vs. low Lp(a).

6/8) So where did all the risk go? It was concentrated in the highest waist-to-hip tertile—a proxy for visceral fat. In that, elevated Lp(a) became a potent risk factor, with individuals being three times more likely to experience a cardiovascular event.

The takeaway is powerful: Lp(a) appears to elevate cardiovascular risk in those with a high waist-to-hip ratio. The empowering message is that even if you can’t change your genetics, you can change your context. Your genes may load the gun, but metabolic health pulls the trigger.

7/8) This begs a critical question: why does visceral fat exert such strong influence on Lp(a) risk? The answer, detailed in the letter, lies in a dangerous synergy. Visceral fat is biologically active, contributing to both inflammation (hsCRP) and clot formation (PAI-1), the very pathways that Lp(a) itself activates.

8/8) In the full deep dive (linked below), I cover all of this and give you the actionable plan: specific optimal waist-to-hip ratio goals for men & women, the role of oxidative stress (OxPLs), and a protocol to reduce visceral fat and otherwise lower risk associated with Lp(a).
staycuriousmetabolism.substack.com/p/why-lpa-may-…