Carotid siphon calcifications are associated with all-cause mortality: Results from the Atahualpa Project.

Abstract

The carotid siphon is the intracranial arterial segment most susceptible to develop atherosclerotic lesions.1 These lesions typically present as calcium deposits in the tunica media and represent a reliable biomarker of intracranial atherosclerotic disease.2 Therefore, carotid siphon calcifications (CSC) may be related to premature mortality. However, studies assessing CSC-related mortality are limited. This cohort study, embedded within the populationbased Atahualpa Project,3 aimed to assess differences in mortality risk according to CSC severity. The Atahualpa Project is a population-based prospective cohort study designed to determine risk factors associated with the increasing burden of noncommunicable neurological and cardiovascular diseases in individuals of Amerindian ancestry living in rural Ecuador.4 For the purposes of the present study, community-dwellers aged ⩾ 40 years (mean age 54.9 ± 12.6 years; 55% women) who received baseline head computed tomography (CT) and clinical interviews were prospectively followed. According to Woodcock et al.,5 CSC Grade 1 were defined as the absence or nearabsence of calcification, Grade 2 as tiny, scattered calcifications, Grade 3 as thick interrupted or thin confluent calcifications, and Grade 4 as thick contiguous calcifications. For simplicity in analyses and based on our previous work,6 individuals were further classified into those with low (Grades 1 and 2) and high (Grades 3 and 4) calcium content in carotid siphons. Cox-proportional hazards models were adjusted for demographics, cardiovascular risk factors (smoking status, body mass index, physical activity, diet, blood pressure, fasting glucose, and total cholesterol blood levels), the presence of strokes at baseline and follow-up, and the regular use of statins over the study years. Cardiovascular risk factors were stratified according to the American Heart Association’s proposed criteria.7 This model was fitted to estimate the mortality hazard ratio (HR) according to CSC severity. All participants signed a comprehensive informed consent at enrolment, and the study was approved by the Ethics Committee of our institution. Medical students continuously visited households where participants live to identify cases with a suspected overt stroke, which was confirmed by a neurologist with the aid of a magnetic resonance image (MRI). In the event of death, certificates were reviewed and verbal autopsies were obtained to ascertain the date and probable cause of death. The last administrative censoring date was set as March 1, 2022. Participants who declined consent and those who emigrated were censored at the last annual survey when the individuals were interviewed, and those who died were censored at the time of death. All these individuals contributed to the total time of follow-up. Of 933 individuals identified during door-to-door surveys, 778 (83%) received a head CT and baseline clinical interviews, and were eligible for this study. The total follow-up of study participants was 4691 (95% CI: 4577– 4806) person-years and the mean follow-up was 6.03 (± 2.09) years. High calcium content in the carotid siphons were determined in 171/778 (22%) individuals. There were several differences in clinical characteristics across individuals with low and high calcium content in the carotid siphons (online Supplemental Table 1). One hundred and eight participants (14%) died during the follow-up, resulting in an overall unadjusted crude mortality rate of 2.3 (95% CI: 1.9–2.8) per 100 person-years. Mortality occurred in 54/607 (9%) individuals with low calcium content and in 54/171 (32%) of those with high Carotid siphon calcifications are associated with all-cause mortality: Results from the Atahualpa Project