Role of bone mineral density in the inverse relationship between body size and aortic calcification: results from the Baltimore Longitudinal Study of Aging

Abstract

Objective: There is a J-shaped relationship between body mass index (BMI) and cardiovascular outcomes in elderly patients (obesity paradox). Whether low BMI correlates with aortic calcification (AC) and whether this association is accounted for by bone demineralization is uncertain.

Methods: Presence of AC was evaluated in 687 community-dwelling individuals (49% male, mean age 67 ± 13 years) using CT images of the thoracic, upper and lower abdominal aorta, and scored from 0 to 3 according to number of sites that showed any calcification. Whole-body bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry. Predictors of AC were assessed by logistic regression, and the role of BMD using mediation analysis.

Results: Age and cardiovascular risk factors were positively associated while both BMI (r = -0.11, p < 0.01) and BMD (r = -0.17, p < 0.0001) were negatively associated with AC severity. In multivariate models, lower BMI (OR 0.96, 95%CI 0.92-0.99, p = 0.01), older age, higher systolic blood pressure, use of lipid-lowering drugs and smoking were independent predictors of AC. A nonlinear relationship between BMI and AC was noticed (p = 0.03), with decreased AC severity among overweight participants. After adjusting for BMD, the coefficient relating BMI to AC was reduced by 14% and was no longer significant, whereas BMD remained negatively associated with AC (OR 0.82, 95%CI 0.069-0.96, p = 0.01), with a trend for a stronger relationship in older participants.

Conclusion: Low BMI is associated with increased AC, possibly through calcium mobilization from bone, resulting in low BMD. Prevention of weight loss and bone demineralization with aging may help reducing AC.

Keywords: Aortic calcification; Body mass index; Body size; Bone mineral density; Calcification paradox; Obesity paradox.

Figure 1. Putative mediation pathway for the relationship between body size, bone mineral density and aortic calcification

A mediator is conceptualized as being within the causal pathway of the predictor and the outcome of interest (A & B above: decreased body size determines a reduction in bone mineral density, which in turn increases aortic calcification). If one ignores the mediator (bone mineral density), one will observe a relationship between the predictor (body size) and the outcome variable (aortic calcification) (C). Adjusting for the mediator results in an attenuation or elimination of the relationship between the predictor and the outcome variable (C*). Numbers in italic represent Spearman correlation coefficients between different body size measures (body mass index, body weight and body height), bone mineral density and aortic calcification severity score. †= p value <0.01.

Figure 2. Nonlinear relationship between body mass index and aortic calcification

The graph shows that the probability of increased aortic calcification severity decreased in participants with overweight as compared to those with normal weight or obesity. Odds ratios (OR) and 95% confidence intervals are adjusted for age, gender, race, systolic blood pressure, antihypertensive medications, LDL cholesterol, lipid-lowering medications, glomerular filtration rate, diabetes and smoke.