Parathyroid hormone and arterial dysfunction in the multi-ethnic study of atherosclerosis

Abstract

Objective: High circulating concentrations of parathyroid hormone (PTH) have been associated with increased risks of hypertension, left ventricular hypertrophy, congestive heart failure and cardiovascular mortality. Impaired arterial function is a potential mechanism for these associations. We tested whether serum PTH concentration is associated with measures of arterial function.

Design: Cross-sectional study.

Participants: A total of 6545 persons without clinical cardiovascular disease participating in the community-based Multi-Ethnic Study of Atherosclerosis.

Measurements: Brachial artery flow-mediated dilation (FMD) as well as aortic pulse pressure and arterial pulse parameters derived from Windkessel modelling of the radial pressure waveform.

Results: Higher serum PTH concentration was associated with lower brachial artery FMD (mean difference -0·09% per 10 pg/ml PTH), higher aortic pulse pressure (0·53 mmHg per 10 pg/ml) and reduced Windkessel capacitive index C1 (large artery elasticity, -0·12 ml/mmHg × 10 per 10 pg/ml), adjusting for potential confounding variables (all P-values ≤ 0·001). These relationships were independent of serum calcium concentration, serum 25-hydroxyvitamin D concentration and estimated glomerular filtration rate and were consistent across relevant participant subgroups. Associations of PTH with aortic pulse pressure and capacitive index C1 were attenuated after adjustment for blood pressure. Serum PTH concentration was not associated with the oscillatory index C2 (small artery elasticity).

Conclusions: Higher serum PTH concentration was associated with impaired endothelial function, increased aortic pulse pressure and decreased capacitive index C1 in a large, diverse, community-based population. These relationships may help explain previously observed associations of elevated PTH with cardiovascular disease.

Figure 1

Associations of PTH concentration with (A) Brachial artery flow mediated dilation, (B) Aortic pulse pressure, (C) Large artery elasticity, and (D) Small artery elasticity. LOWESS smoothed curves on scatter plots. R values are Spearmen correlation coefficients. Analyses included 3,341 participants for flow mediated dilation, 6,042 participants for aortic pulse pressure, and 6,083 participants for large and small artery elasticities.

Figure 2

Stratified analysis of the association of serum parathyroid hormone concentration (PTH) with (A) Brachial artery flow-mediated dilation (FMD) and (B) Aortic pulse pressure. Point estimates are change in mean FMD or mean aortic pulse pressure per 10 pg/ml increment in serum parathyroid hormone concentration. For FMD, left favors stronger association with PTH, and right favors weaker association with PTH. For aortic pulse pressure, left favors weaker association with PTH, and right favors stronger association with PTH. P-values are for interaction of PTH with each subgroup. Analyses included 3,341 participants for flow mediated dilation and 6,042 participants for aortic pulse pressure.