Abstract

BackgroundEvidence has pointed towards differences in the burden of arteriosclerosis according to its location and sex. Yet there is a scarcity of population-based data on aggregated sex-specific cardiovascular risk profiles, instead of single risk factors, and mortality risk according to the location of arteriosclerosis. We assessed sex-specific cardiovascular risk profiles and mortality risk associated with arteriosclerosis.MethodsFrom the population-based Rotterdam Study, 2357 participants (mean age 69 years, 53% women) underwent non-contrast computed tomography to quantify calcification, as a proxy for arteriosclerosis, in the coronary arteries (CAC), aortic arch (AAC), extracranial (ECAC) and intracranial carotid arteries (ICAC), vertebrobasilar arteries (VBAC), and aortic valve (AVC). Principal component analysis (PCA) of eight distinct cardiovascular risk factors was performed, separately for women and men, to derive risk profiles based on the shared variance between factors. We used sex-stratified multivariable logistic regression to examine the associations between PCA-derived risk profiles and severe calcification at different locations. We investigated the associations of severe calcification with mortality risk using sex-stratified multivariable Cox regression.ResultsPCA identified three cardiovascular risk profiles in both sexes: (1) anthropometry, glucose, and HDL cholesterol; (2) blood pressure; and (3) smoking and total cholesterol. In women, the strongest associations were found for profile 2 with severe ECAC and ICAC (adjusted OR [95% CI] 1.32 [1.14–1.53]) and for profile 3 with severe at all locations, except AVC. In men, the strongest associations were found for profile 2 with VBAC (1.31 [1.12–1.52]) and profile 3 with severe AAC (1.28 [1.09–1.51]). ECAC and AVC in women and CAC in men showed the strongest, independent associations with cardiovascular mortality (HR [95% CI] 2.11 [1.22–3.66], 2.05 [1.21–3.49], 2.24 [1.21–3.78], respectively).ConclusionsOur findings further underline the existence of sex- and location-specific differences in the etiology and consequences of arteriosclerosis. Future research should unravel which distinct pathological processes underlie differences in risk profiles for arteriosclerosis.

Highlights

  • Evidence has pointed towards differences in the burden of arteriosclerosis according to its location and sex

  • Within a large prospective population-based cohort, we investigated sex-specific cardiovascular risk profiles associated with arterial calcification, as a proxy for arteriosclerosis, at six different locations

  • The strongest correlation was found between aortic arch (AAC) and extracranial carotid artery calcification (ECAC) and the weakest between vertebrobasilar artery calcification (VBAC) and aortic valve calcification (AVC)

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Summary

Introduction

Evidence has pointed towards differences in the burden of arteriosclerosis according to its location and sex. Arteriosclerosis occurs systemically throughout the arterial system, increasing evidence points towards distinct arteryspecific differences across individuals which is striking when comparing women and men [2,3,4,5] These differences in the burden of arteriosclerosis across arteries and between women and men could be of pathophysiological origin but are likely to reflect underlying differences in modifiable cardiovascular risk factors. Studying risk profiles in an aggregated manner would allow to account for the interaction between various cardiovascular risk factors [11, 12] This could provide insight into the etiology of arteriosclerosis and may eventually contribute to facilitate risk stratification in clinical settings

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