Journal: European journal of preventive cardiology
Study question
Whether lifelong genetic downregulation of the interleukin‑6 receptor (IL6R)—a proxy for IL‑6R blockade—is associated with lower risk of major chronic diseases or increased longevity in postmenopausal women.
Design and population
- – Prospective analysis within the Women’s Health Initiative.
- – 38,807 genotyped participants; 23,464 had the opportunity to reach age 90 by February 19, 2023.
- – IL6R variant: rs8192284 (p.Asp358Ala); carrier status defined by number of variant alleles.
- – Median follow‑up: 20 years.
Endpoints
- – Incident coronary heart disease (CHD), heart failure (HF), stroke, and invasive cancer.
- – Survival to age 90 (yes/no).
- – High-sensitivity CRP (hsCRP) used to stratify inflammatory status (≥2 vs <2 mg/L).
Key results
- – Longevity: 52.0% (12,181/23,464) survived to at least 90 years.
- – No difference in odds of surviving to age 90 for women with two IL6R variant alleles vs non-carriers (OR 1.00; 95% CI 0.91–1.09).
- – IL6R variant carrier status was not associated with risk of CHD, HF, stroke, or invasive cancer.
- – hsCRP ≥2 mg/L was associated with modestly higher all‑cause mortality and CHD risk, but this effect was independent of IL6R carrier status, and no significant interaction was observed.
Implications
- – Lifelong genetic IL6R “blockade” does not appear to reduce major chronic disease incidence or extend survival to very old age in this large, ethnically diverse cohort of postmenopausal women.
- – These genetic data do not suggest major long‑term benefits or harms for longevity or cancer risk related to reduced IL‑6R signaling, despite the therapeutic use of pharmacologic IL‑6R inhibitors in inflammatory disease.