Celermajer · Journal of the American College of Cardiology 1994 · cross-sectional observational study · n=238

Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women.

Cited 1336 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional observational study assessing age-related physiological differences across age groups.

PubMed 8034885 · doi:10.1016/0735-1097(94)90305-0 · record verified 2026-08-28

What was done

High-resolution ultrasound was used to assess brachial artery physiology in 238 healthy subjects (103 men, 135 women; mean age 38 ± 17 years, range 15 to 72) without known cardiovascular risk factors. Researchers measured endothelium-dependent flow-mediated dilation in response to reactive hyperemia and endothelium-independent dilation in response to sublingual glyceryl trinitrate across age groups in men and women.

What was found

In multivariate analysis for the full cohort, reduced flow-mediated dilation was inversely associated with age (r = -0.34, p < 0.0001). In men, flow-mediated dilation remained preserved up to age 40 and declined thereafter at a rate of 0.21%/year. In women, flow-mediated dilation remained stable until the early 50s and then declined at 0.49%/year (p = 0.002 compared with the rate in men). Endothelium-independent dilation to glyceryl trinitrate showed no significant change with aging in either sex.

Why it matters

This study provides physiological evidence that age-related endothelial dysfunction begins approximately a decade earlier in men than in women, aligning with epidemiological patterns of cardiovascular disease onset and the timing of menopause.

Limits

The cross-sectional design infers aging trajectories across different individuals rather than tracking changes longitudinally over time. Hormone levels and menopausal status were not directly measured, relying instead on age as a proxy. Vascular function was evaluated in the peripheral brachial artery rather than coronary circulation.

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