Arterial calcification at multiple sites: sex-specific cardiovascular risk profiles and mortality risk—the Rotterdam Study

Abstract

Background Evidence 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. Methods From 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. Results PCA 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). Conclusions Our 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.

Aortic Arch Calcification Is Associated With Death From Cardiovascular Disease, Infection, and Malnutrition in Patients on Hemodialysis: a Retrospective Cohort Study

“…This result was compatible with a previous report that the incidence of cerebral infarction was associated with calci cation of the thoracic aorta [10]. Moreover, a recent report showed that CVD risk pro les in both sexes that were differentially associated with calci cation at multiple vascular sites [11]. Although gender association was not clear in this study, this report supports the importance of assessing AAC, which is a potential risk factor for CVD.…”

Apolipoprotein E genotype, lifestyle and coronary artery disease: Gene-environment interaction analyses in the UK Biobank population

“…In order to formally test for an interaction, we added an interaction term (on a multiplicative scale) between the (individual) APOE genotypes and the lifestyle factor to the cox proportional hazard model adjusted for the confounders. We acknowledge that lifestyle factors as well as the risk to develop CAD differs between men and women [27], and therefore we additionally stratified the analyses by sex.…”

Arterial calcification at different sites and prediction of atherosclerotic cardiovascular disease among women and men

“…Differing associations between calcification and cardiovascular disease risk depending on the vascular territory have been reported [33,34]. This is likely driven by differences in risk profiles for calcification at multiple sites [8]. The shift in current guidelines from coronary heart disease only towards a broader ASCVD outcome may require to consider assessment of calcification in other arteries than only the coronary arteries.…”

“…Moreover, evidence points towards a varying burden of calcification across various arteries [7,8], translating into differences in coronary heart disease and stroke risk depending on the proximity of the artery to the heart or brain [9,10]. The expanded focus of recent guidelines with the inclusion of stroke raises questions about the value of calcification assessment in other vascular territories for ASCVD risk prediction and stratification, beyond sole assessment of CAC.…”