Thread by @Marion436842126

1/11 Lp(a) is an acute-phase reactant, meaning its production in the liver is upregulated during inflammation, and infections. Statins can increase Lp)a levels, as can mRNA vaccines which induce a controlled immune response, triggering inflammation /2

https://twitter.com/ken_trails/status/1947742911946494197

2/11 to stimulate antibody production.
This is driven by pro-inflammatory cytokines like interleukin-6 which stimulate hepatocytes to increase Lp(a) synthesis. Infections, especially acute ones (e.g., bacterial or viral), trigger systemic inflammation, elevating acute-phase /3

3/11 proteins like (CRP) and Lp(a).
Lp(a) is protective. It binds to bacterial lipopolysaccharides and oxidized phospholipids, potentially neutralizing endotoxins during infections. Lp(a) accumulates at sites of vascular injury, acting as a “repair molecule” by providing /4

4/11 cholesterol or modulating fibrinolysis to stabilize damaged vessels.
Why lower it ? Lp(a) is not causal of heart disease. Insulin Resistance, inflammation and infection are the primary drivers of heart disease, which is why artificially lowering Lp(a)/LDL with any drug /5

5/11 does not prevent cardiovascular disease.
As for Repatha - A 2022 reanalysis of the FOURIER trial raised serious concerns about Evolocumab (Repatha). After readjudication, cardiac deaths were higher in the Repatha group (113 vs. 88 placebo), suggesting cardiac harm. /6

6/11

Specifically, myocardial infarction deaths were up in the Repatha group (36 vs. 25), while placebo had fewer (27 vs. 30). Cardiac failure deaths nearly doubled with Repatha (31 vs. 16). Why the discrepancies ?
/7bmjopen.bmj.com/content/12/12/…

7/11 The trial was ended early after 2.2 years, just as all-cause mortality started favouring placebo.
Why stop early ? . A longer follow-up would have shown a clearer mortality signal. Transparency matters !
FOURIER increased /8

8/11 its sample size from 22,500 to 27,564 candidates mid-trial. Why ? Adding participants diluted emerging trends, like the mortality divergence favoring placebo. Perfect timing !
The data hints at potential harm from Repatha, yet design choices, early termination, sample /9

9/11 size tweak, cloud the picture. We need truly independent scrutiny of the raw data.
Takeaway: Repatha lowers LDL, but FOURIER’s issues (adjudication errors, early end, sample changes) raise red flags about safety. Doctors and patients deserve answers
/10

10/11 Lowering LDL does not prevent heart disease because LDL is not the cause of heart disease. Insulin resistance, inflammation, and infection are the true drivers of cardiovascular disease. FOURIER’s issues highlight the need to rethink lipid-focused treatments
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11/11 Also, the global push to reduce meat and natural saturated fat in the diet, has led to an increase in heart disease. Vilification of fat in the diet overlooks evidence that insulin resistance & chronic inflammation are the critical culprits in CVD progression.