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Progression of Early Subclinical Atherosclerosis (PESA) Study: JACC Focus Seminar 7/8

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⚠️ Auto-extracted by Claude on 2026-06-25 — not verifiable against full text: both the focus-seminar review (Ibanez 2021) and the primary cross-sectional paper (Fernández-Friera 2017) are closed-access (JACC), full text not retrievable. The quantitative results below (49.7% prevalence, OR 1.14–1.18 per 10 mg/dL LDL-C, cohort n’s) are transcribed from the published abstracts and are abstract-confirmed; figure-level and table-level detail are not. gap/no-fulltext-access

PESA — Progression of Early Subclinical Atherosclerosis

The PESA-CNIC-SANTANDER study is a large prospective imaging cohort that established two things this wiki cares about: (1) subclinical atherosclerosis is highly prevalent in middle-aged, asymptomatic adults, and (2) LDL-C is independently associated with plaque even at levels currently considered normal and even in people free of conventional cardiovascular risk factors — the empirical backbone of the primordial-prevention argument for early LDL lowering.

This is the imaging-cohort complement to the genetic (Ference 2012 MR) and intervention (statins, PCSK9 editing) evidence for cumulative-LDL causality on atherosclerosis.

The cohort (Ibanez 2021 focus-seminar review)

PESA enrolled 4,184 asymptomatic middle-aged participants (CNIC employees, Madrid) between 2010 and 2014, with serial 3-yearly follow-up examinations combining clinical interviews, lifestyle questionnaires, biological sampling, and noninvasive multi-territory imaging of subclinical atherosclerosis — carotids, iliofemorals, abdominal aorta (2D/3D vascular ultrasound), and coronaries (coronary artery calcium scoring) 1. A CNIC–Santander Bank joint venture, PESA is designed to track atherosclerosis trajectories from earliest stages through the transition to symptomatic disease, and is expected to run until at least 2029 1.

The design point: treating atherosclerosis as a systemic disease detectable across vascular beds decades before symptoms — the imaging analogue of the “atherosclerosis integrates over decades” cumulative-exposure model.

Headline quantitative finding (Fernández-Friera 2017 primary)

In the PESA sub-analysis restricted to participants free of conventional cardiovascular risk factors (n = 1,779; mean age 45.0 ± 4.1 yr; 50.3% women) 2:

ResultValue
Subclinical atherosclerosis (plaque or coronary calcification) present49.7% of risk-factor-free participants
LDL-C association with atherosclerosis presence/extentindependent of age + sex; OR 1.14–1.18 per 10 mg/dL LDL-C

The authors’ conclusion is the load-bearing one: LDL-C, even at “normal” levels, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major risk factors — supporting more aggressive LDL-C lowering for primordial prevention, not just in conventionally high-risk patients 2.

Why it matters here

  • Plaque before symptoms, plaque before “high” LDL. Nearly half of metabolically “clean” 40-something adults already carry subclinical plaque, and the gradient tracks LDL-C down into the normal range. This is the imaging counterpart to the genetic finding that lifelong lower LDL is disproportionately protective (Ference 2012) — both point at cumulative ApoB-particle exposure as the driver of the atherosclerosis pace.
  • Supports earlier-is-better LDL strategy. Consistent with the ApoB “LDL-years” framework and the geroprotective rationale for durable early LDL reduction (the explicit design argument for one-dose PCSK9 base editing).

Caveats

  • Closed-access; only abstracts confirmable — gap/no-fulltext-access. Per-territory plaque burdens, calcium-score distributions, and the multivariable model internals are not independently checked.
  • Observational cross-sectional association, not a trial — establishes LDL–plaque association in low-risk adults, not that lowering LDL in this group changes outcomes (no event endpoint in the cross-sectional analysis).
  • Single-center, predominantly Spanish working-age cohort; generalizability to other populations/ages is bounded.

Citations

Footnotes

  1. ibanez-2021-pesa-subclinical-atherosclerosis · doi:10.1016/j.jacc.2021.05.011 · Ibanez B, Fernández-Ortiz A, Fernández-Friera L, et al. · JACC 2021;78(2):156–179 · PMID 34238438 · JACC Focus Seminar review of the PESA-CNIC-SANTANDER prospective cohort (n=4,184 asymptomatic middle-aged; enrolled 2010–2014; serial 3-yearly multi-territory imaging; NCT01410318) · model: human · closed-access, abstract-confirmed. ↩ ↩2

  2. doi:10.1016/j.jacc.2017.10.024 · Fernández-Friera L, Fuster V, López-Melgar B, et al. · JACC 2017;70(24):2979–2991 · PMID 29241485 · observational (PESA cross-sectional) · n=1,779 risk-factor-free (of 4,184) · model: human · subclinical atherosclerosis in 49.7% of CVRF-free participants; LDL-C independently associated with plaque presence/extent, OR 1.14–1.18 per 10 mg/dL; supports primordial LDL lowering · closed-access, abstract-confirmed. ↩ ↩2

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