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Objective: To investigate associations among body composition, cardiovascular risk factors, and atherosclerosis in middle-aged and elderly men for the identification of potential pathogenic links., Research Methods and Procedures: The study included 168 white men 44 to 86 years old. Severity of aortic calcification (AC) was graded on lateral radiographs, and body fat and lean mass were measured by DXA. Information on demographic and lifestyle characteristics also was gathered., Results: A strong and independent inverse association was found between AC and peripheral lean mass (PLM), even after adjusting for age and BMI (p < 0.05). Independently of the influence of PLM, AC was directly correlated with truncal fat mass (p < 0.05). Furthermore, AC was inversely associated with tertiles of the free androgen index (p < 0.05). In a multiple regression model, age and serum cholesterol (p < 0.01) contributed directly, and truncal fat mass tended also to contribute directly (p = 0.09), whereas PLM contributed borderline inversely (p = 0.06) to the variation of AC (R = 0.635, p < 0.0001)., Discussion: Severity of AC is strongly dependent on age and further modulated by an array of traditional cardiovascular risk factors. Sarcopenia and truncal fat mass are reciprocal correlates of atherosclerosis of borderline statistical significance in multivariate models. To clarify whether sarcopenia is an atherogenic risk factor or rather a parallel consequence of low-grade inflammation also promoting atherogenic trends, further longitudinal studies in larger sample sizes of men and women are needed.

Objective: To investigate whether aorta calcification (AC) - a surrogate marker of atherosclerosis - is an independent indicator of low bone mass density (BMD), accelerated bone loss, and risk of future fractures in postmenopausal women., Design: A prospective epidemiological study. Follow-up period was 7.5 years., Setting: Community-based sample followed by a research institute., Subjects: A total of 2662 generally healthy postmenopausal women with a mean age of 65.0 +/- 7.1 years at baseline., Main Outcome Measures: Annual rate of changes in BMD (DEXA) and AC (X-rays), vertebral fractures (X-rays), hip fractures (questionnaire)., Results: Advanced AC at baseline was significantly associated with lower BMD and accelerated bone loss from the proximal femur. In a multivariate logistic regression model, age (OR 1.1, 95% CI 1.0-1.2, P = 0.02), body mass index (BMI; OR 0.9, 95% CI 0.8-1.0, P = 0.03) and the severity of AC (OR 2.3, 95% CI 1.1-4.8, P = 0.03) were independent predictors of hip fractures. Adjusted OR for vertebral fracture was 1.2 (95% CI 1.0-1.5, P = 0.12)., Conclusions: Aorta calcification seems to independently contribute to the development of osteoporosis in the proximal femur. Further studies are needed to clarify whether effective atherosclerosis prevention lowers hip fracture risk.

Animal experiments revealed conflicting results as to the impact of bisphosphonate treatment on atherosclerosis and related vascular calcification. The effect of long-term treatment with clinical doses of bisphosphonates on aortic calcification (AC) in an "at-risk" population of osteoporotic elderly women has not been assessed systematically. In the present analysis including 474 women (55-80 years) participating in two 3-year randomized, placebo-controlled clinical trials, we assessed the simultaneous impact of ibandronate given either orally (2.5 mg daily or 20 mg intermittently) or intravenously (0.5 mg or 1.0 mg IV every 3 months) on bone mass and AC. All women received calcium and vitamin D supplements. Bone mineral density (BMD) was measured at the lumbar spine and the total hip using dual-energy X-ray absorptiometry (DXA). Calcified deposits of the lumbar aorta (L1-L4) were visualized on lateral radiographs and severity was graded by a validated scoring system. Measurements were performed at baseline and at years 1, 2, and 3. At baseline, there was a significant inverse correlation between the severity of AC and BMD at the hip (r=-0.151, P=0.003), but not at the lumbar spine. The two oral doses and the 1.0 mg IV dose evoked statistically significant increases in both hip and spine BMD compared with placebo, whereas the effect of 0.5 mg was significant only at the hip (P<0.05). No differences in the yearly rate of progression or the 3-year change in AC was observed between the different intervention groups. Furthermore, there were no statistically significant correlations between the 3-year change in BMD and the simultaneous change in AC. These findings thus suggest that 3-year treatment with effective doses of ibandronate does not pose any cardiovascular risk in terms of altering vascular calcification.

Aim: To investigate the long-term effects of central fat mass (CFM) and peripheral fat mass (PFM) on atherogenic risk profile and the progression of aortic calcification (AC) in postmenopausal women., Methods and Results: Participants were 316 women aged 50-76 years, who were followed for 7.7 years. CFM and PFM were measured at baseline by DXA and related to follow-up measures of atherogenic metabolites, blood pressure, and the progression of AC assessed on lateral radiographs. CFM and PFM independently of each other exhibited contrasting influence on follow-up measures of atherogenic risk factors and the progression of AC. In a multiple regression model, the negative contribution of PFM (P<0.05), but not the adverse contribution of CFM, was independent of confounders. When comparing different extreme forms of obesity, women with central obesity showed the greatest (2.36+/-0.60, n=11), whereas those with peripheral obesity the smallest changes in AC (0.50+/-0.34, n=10) over the study period. Women with general obesity also tended to show less progression of AC compared with women with central obesity (1.23+/-0.42, n=21)., Conclusions: This study provides direct support for the independent anti-atherogenic influence of PFM and calls on further research to define the adipocyte-derived factors involved in this favourable effect.

Previous studies indicate that low bone mineral density (BMD) in the hip is a useful predictor of cardiovascular mortality among the elderly. The objective of this study was to investigate whether low hip BMD is directly associated with the severity of atherosclerosis. The per-protocol population consisted of 963 women aged 60-85 years. Study variables were aortic calcification (AC) graded on lateral lumbar radiographs, BMD at various anatomic sites (distal radius, lumbar spine, proximal femur) measured by DXA, information on various risk factors, and medical history. After adjustment for age, BMD at the proximal femur, but not at the radius or spine BMD, showed statistically significant association with the severity of AC (r = -0.12-17, P < 0.001). Age, years since menopause, BMI, level of education, current and previous smoking, and weekly fitness activity were significant common risk factors (all P < 0.05) with contrasting influence on AC and hip BMD. In a multiple regression model, AC contributed significantly and independently to the variation in hip BMD (beta = -0.10, P = 0.004). Impaired blood flow represented by 40 women with documented history of intermittent claudication was not an independent contributor and did not alter the association between AC and hip BMD. However, AC and demineralization in the hip was particularly severe in women with intermittent claudication accompanied by a higher prevalence of coronary heart disease compared with age-matched controls (all P < 0.001). In conclusion, severe osteoporosis in the hip may indicate advanced atherosclerosis and thereby an increased risk for not only hip fractures but also for coronary heart disease. The results further emphasize that osteoporosis in the hip and peripheral vascular disease are linked by common risk factors and pathomechanisms.