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Background The origins of sex differences in cardiovascular diseases are not well understood. We examined the contribution of childhood risk factors to sex differences in adult carotid artery plaques and intima-media thickness (carotid IMT). Methods and Results Children in the 1985 Australian Schools Health and Fitness Survey were followed up when they were aged 36 to 49 years (2014-19, n=1085-1281). Log binomial and linear regression examined sex differences in adult carotid plaques (n=1089) or carotid IMT (n=1283). Childhood sociodemographic, psychosocial, and biomedical risk factors that might contribute to sex differences in carotid IMT/plaques were examined using purposeful model building with additional adjustment for equivalent adult risk factors in sensitivity analyses. Women less often had carotid plaques (10%) than men (17%). The sex difference in the prevalence of plaques (relative risk [RR] unadjusted 0.59 [95% CI, 0.43 to 0.80]) was reduced by adjustment for childhood school achievement and systolic blood pressure (RR adjusted 0.65 [95% CI, 0.47 to 0.90]). Additional adjustment for adult education and systolic blood pressure further reduced sex difference (RR adjusted 0.72 [95% CI, 0.49 to 1.06]). Women (mean±SD 0.61±0.07) had thinner carotid IMT than men (mean±SD 0.66±0.09). The sex difference in carotid IMT (β unadjusted -0.051 [95% CI, -0.061 to -0.042]) reduced with adjustment for childhood waist circumference and systolic blood pressure (β adjusted -0.047 [95% CI, -0.057 to -0.037]) and further reduced with adjustment for adult waist circumference and systolic blood pressure (β adjusted -0.034 [95% CI, -0.048 to -0.019]). Conclusions Some childhood factors contributed to adult sex differences in plaques and carotid IMT. Prevention strategies across the life course are important to reduce adult sex differences in cardiovascular diseases.

Abstract: Introduction: We studied the determinants of carotid atherosclerosis in urban-dwelling Australian Aboriginals at high risk of atherosclerotic mortality and morbidity. Methods: Cross-sectional study of self-selected adult Australian Aboriginals. Participants (n =602) aged 18–74 years had risk factor assessment and carotid ultrasound to determine carotid intima-medial thickness (IMT) and the presence of plaque. The upper quartile (>0.71mm in males and >0.62mm in females) was used as a measure of increased carotid IMT. Results: Over 80% of participants were overweight or obese; the prevalence of diabetes was 25%. Age was the major predictor of thick IMT, OR 3.0 (95% CI 2.0–4.5) per decade for males and OR 6.3 (3.3–12.0) for females. Waist circumference and blood glucose were independent predictors of IMT for men, with hypertension, pack-years of smoking, diabetes, and cholesterol ratio additional predictors for women. Plaque was highly prevalent (>40%) in this relatively young population and was predicted by increasing age, a history of smoking and total cholesterol/HDL ratio, but not sex. Conclusions: Urban-dwelling Aboriginal Australians are at increased risk for early atherosclerosis. In this study an excess of obesity-related cardiovascular risk factors were the important contributors to increased IMT carotid atherosclerosis, but not inflammatory markers or other novel risk factors. [Copyright &y& Elsevier]