Calcification of the splenic, iliac, and breast arteries and risk of all-cause and cardiovascular mortality

Background and aims CVD risks associated with coronary artery calcification (CAC) and aortic calcification (AC) are well known, but less is known about other calcified arteries. We aimed to assess the associations of arterial calcification in the breast, splenic, and internal and external iliac arteries with CVD risk factors and mortality. Methods We conducted a case-cohort study nested in a cohort of 5196 individuals who self-referred or were referred by a health care provider for whole body computed tomography (CT), including a random subcohort (n = 395) and total and CVD mortality cases (n = 298 and n = 90), who died during a median follow-up of 9.4 years. Arterial calcification in the breast, splenic, and internal and external iliac arteries on CT was scored using a simple visual score. AC and CAC were previously measured using the Agatston technique. Logistic regression models were made to study associations of CVD risk factors with calcification in the different vascular beds. Prentice-weighted Cox proportional hazards models adjusted for CVD risk factors, and calcification in other vascular beds, were used to study associations with mortality. Results In the subcohort, the mean age was 56.6 years (SD 11.1) and 41.3% were female. The prevalence of calcification on CT, was 11.6% in the splenic, 47.9% in the internal iliac and 9.5% in the external iliac arteries, while 3.7% of women had breast artery calcification (BAC). Calcification in the splenic and iliac arteries was associated with calcification in the abdominal aorta but differentially associated with other CVD risk factors in logistic regression models. The prevalence of BAC was too low to fit these multivariable models. Calcification of the external iliac arteries was significantly associated with both all-cause and CVD mortality, but no longer significant when adjusted for CVD risk factors. Breast artery calcification was associated with both all-cause and CVD mortality independent of CVD risk factors and AAC and CAC (all-cause HR 5.67 [95% CI 1.50–21.41]). Conclusions Risk factors associated with calcification, and the association of calcification with risk of mortality differ across vascular beds, possibly reflecting different pathophysiology

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation