Uppsala, Sweden - A new analysis of a Swedish study of elderly men
has found that plasma parathyroid hormone (PTH) levels predict
cardiovascular mortality, even in those with normal levels of this hormone
[1]. Dr Emil Hagström (Uppsala Clinical Research Center, Sweden) and
colleagues publish their findings in the June 2, 2009 issue of Circulation.
Hagström explained to heartwire that previous studies of this kind have
looked at patients with diseases of mineral metabolism and that it is
recognized that such patients—those with elevated PTH levels resulting from
primary or secondary hyperparathyroidism—are at higher risk for
cardiovascular morbidity and mortality.
But the association they found between CV death and PTH levels among those
with normal levels of the hormone "was unexpectedly strong and similar to
that seen in those with hyperparathyroidism," he notes. The risk of CV death
associated with PTH levels was also similar in magnitude to that of other
risk factors, such as smoking and diabetes, he added.
But whether PTH is a causal factor or whether PTH levels merely reflect
other abnormalities along the mineral metabolism pathway that predispose to
a higher risk for cardiovascular mortality cannot be answered by these
observational data, he notes. But "regardless of where in the chain it is, [PTH]
may still help to improve classical risk prediction models, to sharpen
them," says Hagström.
Findings will need to be replicated and validated
Using data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a
community-based cohort of men with a mean age of 71, Hagström et al
investigated the association between plasma PTH levels and cardiovascular
mortality. During a median of 10 years of follow-up, 117 of the 958
participants died of cardiovascular causes.
In multivariate adjustment models, higher plasma PTH was associated with a
higher risk for CV mortality (HR for one standard-deviation increase in PTH
1.38; p<0.001). This association remained essentially unaltered in those
without previous CVD and in those with normal PTH (<6.8 pmol/L) with no
other signs of a disturbed mineral metabolism, say the researchers.
Elevated plasma PTH (>5.27 pmol/L) accounted for 20% of the
population-attributable risk proportion for cardiovascular mortality,
indicating that the findings could have substantial public-health
implications, Hagström said.
But they emphasize that their new findings "should not be construed as
implying a direct benefit of a reduction of PTH lowering in the primary
prevention of cardiovascular disease in the community." Future research will
be needed to answer this question, and the current findings will need to be
validated and replicated in women, in younger populations, and in other
ethnic groups, they say.
Ongoing randomized trials are examining whether a reduction in PTH levels by
calcimimetic treatment will reduce the incidence of cardiovascular events in
patients with secondary hyperparathyroidism caused by renal failure, the
researchers note.