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.

Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels

“…The increase of carotid wall thickness is at the basis of arterial stiffening and loss of elasticity [22,23]. Arterial stiffening is one of the hallmarks of vascular aging, and is an important risk factor for cardiovascular morbidity and mortality [24][25][26][27][28]. Recent evidences suggest that arterial stiffness accelerates within 1 year of the final menstrual period [29]; therefore, subclinical atherosclerosis is progressive and aggressive in postmenopausal women; thus, increasing their cardiovascular risk.…”

Oestrogen Inhibits Arterial Calcification by Promoting Autophagy

“…The process of transdifferentiation of VSMCs to the osteogenic phenotype plays a crucial role in arterial calcification 36 . Epidemiological studies have shown that the incidence of aortic calcification is intimately related to low bone mineral density in postmenopausal women; this phenomenon is known as the calcification paradox 37 , 38 . These studies suggest that oestrogen plays an important role in the development of arterial calcification.…”

MICS, an easily ignored contributor to arterial calcification in CKD patients

“…Similarly, clinical studies demonstrated that Mg therapy significantly suppressed PTH secretion in CKD, which in turn prevented the development of uremic bone diseases and AC (41,62). Moreover, low BMI was associated with increased AC, possibly through calcium mobilization from bone, resulting in decreased bone mineral density (10).…”