Parathyroid hormone and arterial dysfunction in the <scp>m</scp>ulti‐<scp>e</scp>thnic <scp>s</scp>tudy of <scp>a</scp>therosclerosis

Bosworth, Cortney; Sachs, Michael; Duprez, Daniel; Hoofnagle, Andrew N.; Ix, Joachim H.; Jacobs, David R.; Peralta, Carmen A.; Siscovick, David S.; Kestenbaum, Bryan

doi:10.1111/cen.12163

Cited by 72 publications

(56 citation statements)

References 39 publications

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“…This suggestion would suggest a biological role for PTH in promoting symptoms of HF and consequently BNP expression, 7,14,15,37,38 but this is speculative. PTH has been associated with NT-proBNP in this and other studies.…”

Section: Pth and Incident Hfmentioning

confidence: 99%

Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Wannamethee

Welsh

Papacosta

et al. 2014

Circ: Heart Failure

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Background-Hyperparathyroidism and low vitamin D status have been implicated in the pathogenesis of heart failure (HF).We examined the prospective associations between parathyroid hormone (PTH), circulating 25-hydroxyvitamin D, and markers of mineral metabolism and risk of incident HF in older men with and without established cardiovascular disease. Methods and Results-Prospective study of 3731 men aged 60 to 79 years with no prevalent HF followed up for a mean period of 13 years, in whom there were 287 incident HF cases. Elevated PTH (≥55.6 pg/mL; top quarter) was associated with significantly higher risk of incident HF after adjustment for lifestyle characteristics, diabetes mellitus, blood lipids, blood pressure, lung function, heart rate, renal dysfunction, atrial fibrillation, forced expiratory volume in 1 second, and C-reactive protein (hazards ratio, 1.66; 95% confidence interval, 1.30-2.13). The increased risk was seen in both men with and without previous myocardial infarction or stroke (hazards ratio, 1.72; 95% confidence interval, 1.07-2.76; hazards ratio, 1.70; 95% confidence interval, 1.25-2.30, respectively). Elevated PTH was significantly associated with N-terminal probrain natriuretic peptide, a marker of left ventricular wall stress. By contrast, 25-hydroxyvitamin D and other markers of mineral metabolism including serum calcium and phosphate showed no significant association with incident HF after adjustment for age. Conclusions-Elevated PTH, but not 25-hydroxyvitamin D or other markers of mineral metabolism, is associated with increased risk of HF in both older men with and without myocardial infarction/stroke. This increased risk was not explained by its association with known risk factors for HF. Further studies are now needed to elucidate the mechanisms underlying this association. (Circ Heart Fail. 2014;7:732-739.)

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Section: Pth and Incident Hfmentioning

confidence: 99%

Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Wannamethee

Welsh

Papacosta

et al. 2014

Circ: Heart Failure

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“…PTH may therefore serve a role in the pathophysiology of cardiovascular disease (13). A series of previous studies (14,15) have suggested that PTH may directly induce endothelial dysfunction and contribute to VC. However, the underlying mechanisms of this remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

Cheng

Ling³

et al. 2017

Exp Ther Med

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Abstract. Vascular calcification (VC) occurs in patients with chronic kidney disease (CKD) and contributes to cardiovascular dysfunction and mortality. Parathyroid hormone (PTH) is a crucial regulator of VC. High PTH serum levels constitute as a major risk factor for patients with CKD. However, the effect and mechanism of PTH on osteoblastic differentiation in endothelial cells have not been fully elucidated. In the present study, the role of PTH in VC was investigated using an in vitro calcification model. Endothelial cells were stimulated with PTH in the femto-to picomolar range. As determined by western blot analysis and ELISA, osteoblastic differentiation, as indicated by the BMP2 marker, occurred with maximum effect at 1x10 -10 mmol/l PTH. The results indicate that PTH promotes osteoblastic differentiation of endothelial cells, as demonstrated by the increased expression of bone morphogenetic protein (BMP) 2 and BMP4. In addition, western blot analysis revealed that PTH activated the extracellular signal-regulated protein kinase (Erk)1/2 and nuclear factor (NF)-κB signaling pathways. However, reverse transcription-quantitative polymerase chain reaction demonstrated that inhibitors specific to Erk1/2 and NF-κB eradicated the effect of PTH treatment on BMP2, BMP4, ALP and RUNX2 expression. These results demonstrate that PTH promotes the osteoblastic differentiation of endothelial cells via the Erk1/2 and NF-κB signaling pathways, which suggests a potential role of PTH in the promotion of VC. These findings provide an insight into the association between PTH and cardiovascular disease.

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“…32,33 In a sample of more than 3000 individuals free from major cardiovascular with a wide range of ages (mean age of 62 years), researchers from MESA showed positive association of PTH with arterial stiffness measured by aortic pulse pressure. However, the Health ABC study, which has an older population with a mean age of 72 years, did not find any association between PTH and aortic pulse wave velocity.…”

Section: Discussionmentioning

confidence: 99%

Enhanced parathyroid hormone levels are associated with left ventricle hypertrophy in very elderly men and women

Soares

Freitas

Japiassú

et al. 2015

Journal of the American Society of Hypertension

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

Cited by 72 publications

References 39 publications

Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Elevated Parathyroid Hormone, But Not Vitamin D Deficiency, Is Associated With Increased Risk of Heart Failure in Older Men With and Without Cardiovascular Disease

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

Enhanced parathyroid hormone levels are associated with left ventricle hypertrophy in very elderly men and women

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