Inflammation now predicts heart disease more strongly than cholesterol

Original Article ↗ Hacker News Discussion ↗

Shift from Cholesterol to Inflammation (hs‑CRP)

  • Commenters highlight that ACC now recommends high‑sensitivity CRP (hs‑CRP) for everyone, not just high‑risk patients.
  • Explanation offered: widespread statin use has “normalized” LDL in many patients, so residual risk now shows up more clearly in non‑traditional markers like hs‑CRP.
  • Several note hs‑CRP has long been a standard inflammation biomarker; the “news” is its elevation to guideline status rather than the concept itself.

How Cholesterol, ApoB, Lp(a) and Inflammation Interact

  • Many emphasize ApoB as a better measure than LDL‑C because each atherogenic particle (LDL, VLDL, IDL, Lp(a)) carries one ApoB.
  • Inflammation is framed as additive, not a replacement: plaque formation needs atherogenic particles and an inflamed or damaged arterial wall.
  • Lp(a) is discussed as a largely genetic, independent risk factor; new Lp(a)‑lowering drugs and IL‑6–targeting agents are in late‑stage trials.

Statins, LDL Causality, and Ongoing Disputes

  • One camp stresses very strong evidence that lowering LDL (via statins, PCSK9 inhibitors, ezetimibe, etc.) reduces ASCVD events and all‑cause mortality, backed by RCTs and Mendelian randomization.
  • A skeptical minority questions whether LDL is causal vs a proxy, arguing inflammation or oxidized LDL are the “real” problem and pointing to publication bias and industry incentives.
  • There is debate over statin side‑effects: some report significant muscle or GI issues; others cite meta‑analyses suggesting serious myotoxicity is rare and most reported muscle pain is not drug‑related.

What Lowers Inflammation? (Lifestyle and Drugs)

  • Frequently mentioned non‑drug levers: Mediterranean/DASH‑style diets, weight loss, regular exercise (including walking), good sleep, stress reduction, smoking cessation, and minimizing ultra‑processed foods and environmental irritants.
  • Some discuss aspirin, NSAIDs, corticosteroids, GLP‑1 agonists, and future IL‑6 or Lp(a)-targeted drugs, while warning about GI risks and trade‑offs.
  • Exercise is described as acutely pro‑inflammatory but chronically anti‑inflammatory; overtraining is noted as a risk.

Testing, Panels, and Commercial Concerns

  • Practical questions: whether hs‑CRP replaces or adds to cholesterol testing (consensus: it’s additive), cost and insurance coverage, and whether to order tests directly (Labcorp, Goodlabs, private labs) vs through physicians.
  • The article’s company‑branded panel ($190) is compared against cheaper à‑la‑carte lab options; some see value in bundled MD interpretation, others view it as upselling.
  • Calcium scoring and advanced lipid testing (ApoB, Lp(a), fractionation) are discussed as ways to refine risk beyond standard lipid panels.

Edge Cases and Personal Anecdotes

  • Several share cases of:
    • Early myocardial infarction despite seemingly good lipids and lifestyle, often with strong family history.
    • Very high LDL but zero coronary calcium and no apparent plaque, sometimes in lean low‑carb adherents.
    • Chronic inflammatory conditions (IBD, psoriasis, Crohn’s) treated with biologics, raising questions about net cardiovascular impact.

Broader Debates on Evidence and “Authority”

  • Long subthreads argue over the role of expert consensus vs individual critical reading of the literature, with accusations of “appeal to authority” on one side and “cholesterol denialism” on the other.
  • Some propose alternative or adjunctive mechanisms (endotoxin from the gut, bacterial biofilms in plaques, oxidative stress) as unifying explanations linking inflammation, lipids, and heart disease.
  • A small fringe attributes rising inflammation focus to COVID vaccines; this is not substantiated or developed in the thread.