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(Circulation. 2009;119:2765-2771.)
© 2009 American Heart Association, Inc.

Epidemiology

Plasma Parathyroid Hormone and the Risk of Cardiovascular Mortality in the Community

Emil Hagström, MD, PhD; Per Hellman, MD, PhD; Tobias E. Larsson, MD, PhD; Erik Ingelsson, MD, PhD; Lars Berglund, MSc, PhD; Johan Sundström, MD, PhD; Håkan Melhus, MD, PhD; Claes Held, MD, PhD; Lars Lind, MD, PhD; Karl Michaëlsson, MD, PhD; Johan Ärnlöv, MD, PhD

From Uppsala Clinical Research Center (E.H., L.B., C.H., K.M.), Department of Surgical Sciences, (E.H., P.H., K.M.), Department of Public Health and Caring Sciences/Geriatrics (E.I., J.Ä.), and Department of Medical Sciences (T.E.L., J.S., H.M., L.L.), Uppsala University, Uppsala; Departments of Medical Epidemiology and Biostatistics (E.I) and Nephrology (T.E.L.), Karolinska Institutet, Stockholm; and the Department of Health and Social Sciences (J.Ä.), Högskolan Dalarna, Falun, Sweden.

Correspondence to Emil Hagström, MD, PhD, Uppsala Clinical Research Center, Uppsala University, SE-751 85 Uppsala, Sweden. E-mail emil.hagstrom{at}ucr.uu.se

Received July 25, 2008; accepted March 26, 2009.

Background— Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking.

Methods and Results— The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL · min^–1 · 1.73 m^–2 and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality.

Conclusions— Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

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