Arterial stiffening relates to arterial calcification but not to noncalcified atheroma in women. A twin study

Abstract

Objectives: Our aim was to examine the relationship of arterial stiffness to measures of atherosclerosis, arterial calcification, and bone mineral density (BMD); the heritability of these measures; and the degree to which they are explained by common genetic influences.

Background: Arterial stiffening relates to arterial calcification, but this association could result from coexistent atherosclerosis. A reciprocal relationship between arterial stiffening/calcification and BMD could explain the association between cardiovascular morbidity and osteoporosis.

Methods: We examined, in 900 women from the Twins UK cohort, the relationship of carotid-femoral pulse wave velocity (cfPWV) to measures of atherosclerosis (carotid intima-media thickening; carotid/femoral plaque), calcification (calcified plaque [CP]; aortic calcification by computed tomography, performed in subsample of 40 age-matched women with low and high cfPWV), and BMD.

Results: The cfPWV independently correlated with CP but not with intima-media thickness or noncalcified plaque. Total aortic calcium, determined by computed tomography, was significantly greater in subjects with high cfPWV (median Agatston score 450.4 compared with 63.2 arbitrary units in subjects with low cfPWV, p = 0.001). There was no independent association between cfPWV and BMD. Adjusted heritability estimates of cfPWV and CP were 0.38 (95% confidence interval: 0.19 to 0.59) and 0.61 (95% confidence interval: 0.04 to 0.83), respectively. Shared genetic factors accounted for 92% of the observed correlation (0.38) between cfPWV and CP.

Conclusions: These results suggest that the association between increased arterial stiffness and the propensity of the arterial wall to calcify is explained by a common genetic etiology and is independent of noncalcified atheromatous plaque and independent of BMD.

Figure 1

Path Diagram of Bivariate Genetic Model for PWV and Calcified Plaque, Including Genetic and Environmental Correlations Results for the ACE model are displayed in italic and for the AE model in bold italics (with 95% confidence intervals). A = additive genetic; C = shared environment; E = nonshared environment. Squares = observed variables; circles = latent variable; single-headed arrows = causal paths; and double-headed arrows = correlations.