Hak · Annals of internal medicine 2000 · Population-based cross-sectional study · n=1149

Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.

Cited 1356 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional population study

PubMed 10681281 · doi:10.7326/0003-4819-132-4-200002150-00004 · record verified 2026-08-28

What was done

A population-based cross-sectional study evaluated 1,149 postmenopausal women (mean age 69.0 ± 7.5 years) participating in the Rotterdam Study in the Netherlands. Baseline data were collected on thyroid status (subclinical hypothyroidism defined as TSH > 4.0 mU/L and normal free T4 of 11–25 pmol/L; positive thyroid peroxidase antibodies defined as > 10 IU/mL), aortic atherosclerosis, and history of myocardial infarction, with multivariable adjustment for age, BMI, cholesterol, blood pressure, smoking, and beta-blocker use.

What was found

Subclinical hypothyroidism was present in 10.8% of women and was associated with increased prevalence of aortic atherosclerosis (age-adjusted OR 1.7, 95% CI 1.1–2.6) and myocardial infarction (OR 2.3, 95% CI 1.3–4.0). Risk estimates remained consistent after adjusting for BMI, total and HDL cholesterol, blood pressure, smoking status, and beta-blocker exclusion. The association was stronger in women with both subclinical hypothyroidism and thyroid peroxidase antibodies (aortic atherosclerosis OR 1.9, 95% CI 1.1–3.6; myocardial infarction OR 3.1, 95% CI 1.5–6.3). Thyroid autoimmunity alone showed no association with cardiovascular disease.

Why it matters

This study shows that subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in postmenopausal women, with an attributable risk comparable to major cardiovascular risk factors.

Limits

The cross-sectional design cannot establish temporality or causality. The population was restricted to older postmenopausal women from one Dutch district, limiting generalizability to men, younger populations, or diverse ethnic groups. Longitudinal cardiovascular incidence was not evaluated.

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