Download Relation Between Low Calcium Intake, Parathyroid

Relation Between Low Calcium Intake, Parathyroid
Hormone, and Blood Pressure
Rolf Jorde, Johan Sundsfjord, Egil Haug, Kaare H. Bønaa
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Abstract—In a population health survey in 1995, serum parathyroid hormone (PTH) was measured in 1113 subjects, aged
30 to 79 years, and was found to be elevated (⬎6.9 pmol/L) in 118 subjects. In 1998, this group and 131 subjects with
normal PTH levels were invited for reexamination, and 82 and 90 subjects from each respective group attended the
follow-up. At the follow-up, 72 subjects had elevated and 100 had normal serum PTH levels. Those with elevated serum
PTH levels (8 subjects with hyperparathyroidism were excluded) had significantly lower serum calcium levels and
intake of calcium than those with normal PTH (2.24⫾0.09 and 2.29⫾0.10 mmol/L [mean⫾SD] and 400.3⫾227.3 and
592.1⫾459.6 mg/d, respectively; P⬍0.01). Serum levels or intake of vitamin D did not differ between the 2 groups.
Subjects with elevated PTH in both 1995 and 1998 had significantly lower bone mineral content and bone mineral
density in the lumbar spine than did those with persistently normal PTH levels (P⬍0.05). In the females, but not in the
males, the systolic and diastolic blood pressures were significantly higher in those with elevated serum PTH
(158.0⫾27.5 versus 141.5⫾19.2 mm Hg and 90.5⫾13.6 versus 82.6⫾8.6 mm Hg, respectively; P⬍0.01). This
difference was even more pronounced when those with persistently elevated PTH were considered separately. In
conclusion, reduced intake of calcium is frequently associated with high levels of serum PTH. This is associated with
moderately reduced bone mineral content and bone mineral density in the lumbar spine. In women, high levels of serum
PTH are also associated with markedly increased blood pressure. (Hypertension. 2000;35:1154-1159.)
Key Words: blood pressure 䡲 calcium 䡲 parathyroid hormones 䡲 vitamins
T
D, and PTH participate in bone metabolism, we also compared blood pressure (BP), bone mineral content (BMC), and
bone mineral density (BMD) between subjects with elevated
and normal PTH levels.
he serum calcium level is tightly regulated by the
parathyroid hormone (PTH). Thus, a small decrease in
serum calcium elicits a prompt increase in the secretion of
PTH, which in turn mobilizes calcium from the skeleton and
increases the renal tubular reabsorption of calcium. Furthermore, PTH stimulates the hydroxylation of 25hydroxyvitamin D to the more biologically potent 1,25dihydroxyvitamin D in the kidneys,1 which again leads to an
increased absorption of calcium from the intestine. This
negative-feedback system keeps the serum calcium within
fairly narrow limits.1 Therefore, an increased PTH level may
be caused not only by primary hyperparathyroidism but also
by factors tending to reduce the serum calcium level, like
vitamin D deficiency.2,3
In Tromsø, northern Norway, there have been 4 large
health surveys since 1974.4 In the last survey, which took
place in 1994 to 1995, serum PTH was measured in a
subgroup of 1113 subjects and was found to be elevated in
118. The purpose of the present study was to reexamine the
subjects with an elevated serum PTH and to look for possible
causes of the PTH elevation, in particular the intakes and
serum levels of calcium and vitamin D.
Furthermore, because a high serum PTH level has been
associated with hypertension5– 8 and because calcium, vitamin
Methods
Subjects and Study Protocol
The Tromsø study is a general health survey in the Tromsø area,
northern Norway.4 In the fourth survey, which took place in 1994
and 1995, 27 180 men and women participated. All subjects who
were examined between March 21 and May 19, 1995, and who were
between the ages of 30 and 79 years (a total of 1113 subjects) had
blood samples drawn for the measurement of PTH. One hundred
eighteen of these subjects had PTH values ⬎6.9 pmol/L. In 1998,
these subjects and an age- and gender-matched group (drawn from
the cohort that had a PTH measurement ⬍7.0 pmol/L in 1995) were
invited to participate in a follow-up study.
The follow-up study was performed at the Clinical Research Unit
at the University Hospital of Tromsø. After a general health
examination, a medical history was taken, and present medication
was recorded. All subjects filled out a questionnaire on dietary habits
that included questions on daily use of calcium and vitamin D
tablets. By use of a Norwegian food table,9 the daily intakes of
calcium and vitamin D were calculated.
Received September 7, 1999; first decision September 28, 1999; revision accepted December 21, 1999.
From the Department of Medicine (R.J.) and the Department of Clinical Chemistry (J.S.), University Hospital of Tromsø, Tromsø, Norway; The Centre
of Clincal Epidemiology and Biostatistics (R.J.), Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, Australia; The Hormone
Laboratory (E.H.), Aker University Hospital, Oslo, Norway; and The Institute of Community Medicine (K.H.B.), University of Tromsø, Tromsø, Norway.
Correspondence to Dr Rolf Jorde, Medical Department, University Hospital of Tromsø, 9038 Tromsø, Norway. E-mail [email protected]
© 2000 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
1154
Jorde et al
Measurements
Height, weight, and BP were measured as previously described.10
BMC and BMD were measured with a Lunar DPX-L Dual-Energy
X-ray Absorptiometer (software version 1.3, Lunar Radiation Corp).
Blood samples were analyzed for serum calcium and creatinine
with the use of a Hitachi 917 with reagents from BoehringerMannheim. PTH was measured by an Immulite intact PTH assay
(Diagnostic Products Corp). 25-Hydroxyvitamin D3 was measured as
previously described.11 The interassay coefficients of variation for
these 4 assays were 2.0%, 2.5%, 6% to 8%, and 7% to 12%,
respectively.
Statistical Analyses
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Comparisons between the groups with elevated and normal PTH
levels regarding intake and serum levels of calcium and vitamin D,
as well as body mass index (BMI), were performed with linear
regression, with the parameter in question as a dependent variable,
gender and PTH group (elevated/normal) as fixed factors, and age as
a covariable. Comparisons regarding BP, BMC, and BMD were
performed similarly, with BMI added as a covariable. The same
analyses were repeated in males and females separately. In addition,
a gender-specific multiple linear regression model was used to assess
independent predictors of serum PTH concentration, systolic and
diastolic BP, BMC, and BMD. Age, BMI, serum calcium and
25-hydroxyvitamin D3, and intake of calcium and vitamin D were
included as independent variables in the model. The regression
coefficient is given as the standardized ␤ coefficient (the coefficient
of the independent variables when all variables are expressed in
standardized [z score] form). Comparison of BP between groups
according to combinations of high or low serum PTH levels in 1995
and 1998 was performed by ANOVA with least significant difference as a post hoc test. All tests were 2-sided, and a value of P⬍0.05
was considered statistically significant. Unless otherwise stated, the
data are presented as mean⫾SD. Statistical analyses were performed
with the SPSS version 9.0 (SPSS Inc).
Low Calcium Intake, High Serum PTH, and BP
1155
Possible Causes of Elevated PTH Levels
at Follow-Up
Among the 72 subjects with elevated serum PTH levels at
follow-up, 1 male and 7 females were considered to have
hyperparathyroidism (serum PTH ⬎6.9 pmol/L together with
serum calcium ⬎2.55 mmol/L). Their mean⫾SD age was
70.0⫾7.8 years; systolic and diastolic BP, 156.0⫾9.5 and
90.5⫾11.9 mm Hg, respectively; and BMC at the lumbar
spine, femoral neck, Ward’s triangle, and trochanter,
57.5⫾14.6, 4.1⫾0.7, 2.0⫾0.6, and 10.2⫾3.3 g, respectively.
These 8 subjects are not included in the following analyses.
Mean serum calcium was significantly (P⬍0.01) lower in
the group with high serum PTH levels, whereas mean serum
25-hydroxyvitamin D3 did not differ significantly between the
2 groups (Table 1). The intake of calcium was significantly
(P⬍0.01) lower in those with elevated PTH levels (Tables 1
and 2). In 8 (12.5%) of those with elevated serum PTH, the
intake was ⬍200 mg/d, and in 36 (56.3%) of those with
elevated serum PTH, the intake was ⬍400 mg/d. The corresponding numbers in those with normal PTH levels were 9
(9.0%) and 39 (39.0%), respectively.
The 2 groups did not differ significantly regarding vitamin
D intake (Table 1). None had a serum creatinine
⬎150 ␮mol/L, and none had gastric or bowel resection,
celiac disease, or other known causes of malabsorption. None
were using anticonvulsant drug therapy or other medication
known to affect the PTH levels.
In the multiple linear regression model, the intake of
calcium was significantly (P⬍0.01) associated with serum
PTH in the females but not in the males (Table 3).
Blood Pressure
Ethical Issues
The study was approved by the regional ethics committee, and all
subjects gave written informed consent to participate.
Results
Of the initial 118 subjects with serum PTH levels ⬎6.9
pmol/L in 1995, 1 had died, and 2 had moved from the
Tromsø area. The hospital records of the remaining subjects
were reviewed, and 10 were considered too sick or otherwise
unfit to participate. Three subjects were aged ⬎80 years and
were not invited to participate for that reason. One person had
undergone an operation for hyperparathyroidism, thus leaving
101 subjects that were invited to the follow-up study. Of
these, 10 did not respond to the invitation, and 9 were
unwilling to participate. Of the 82 subjects finally examined,
26 (31.7%) subjects had normal serum PTH levels at followup, and 56 (68.3%) subjects had elevated PTH levels at
follow-up.
From the cohort with serum PTH ⬍7.0 pmol/L in 1995,
131 gender- and age-matched subjects were invited to a
follow-up examination. Ninety subjects were willing to participate and completed the examinations. Of these, 74
(82.2%) subjects had normal serum PTH levels at follow-up,
and 16 (17.8%) subjects had serum PTH levels ⬎6.9 pmol/L
at follow-up.
Thus, at follow up, PTH levels were elevated in a total of
72 subjects and normal in 100 subjects.
Both systolic and diastolic BPs were significantly (P⬍0.05)
higher in the group with elevated PTH levels (Table 1).
However, a significant difference in BP was seen in females
only (P⬍0.01, Table 2). In the females, slightly more subjects
with high serum PTH levels were on BP medication than
those with normal serum PTH (29.0% and 24.1%, respectively). After exclusion of those on BP medication, the difference
in BP was still significant (P⬍0.01, Table 2). The difference
in BP was even more pronounced when those who had
elevated serum PTH levels in both 1995 and 1998 were
considered separately from those who had normal serum PTH
levels on both occasions (Table 4).
In the multiple linear regression model, only serum PTH
reached statistical significance (P⬍0.001) as an individual
predictor for systolic and diastolic BP. However, this was
seen in females only (Table 3).
Because BMI was higher in the group with elevated serum
PTH, the difference in BP between females with high and
normal serum PTH levels at follow-up is shown stratified for
BMI quartiles (BMI ⱕ23.0, 23.1 to 25.7, 25.8 to 28.6, and
⬎28.6 kg/m2) in Figure 1.
BMC and BMD
BMC and BMD were similar in the 2 serum PTH groups
(Table 1). In the multiple linear regression model, BMI was
a significant (P⬍0.001) predictor of BMC and BMD in the
females but not in the males. For the females, this was seen
1156
Hypertension
May 2000
TABLE 1. Characteristics of Those With Normal and High Serum PTH in 1998
and Main Results
PTH in 1998
Variables
Reference Range
Men/women, n/n
Age, y
46/54
䡠䡠䡠
68.9⫾7.6
69.4⫾9.4
82.5⫾16.1
82.1⫾16.3
4.5⫾1.2
9.1⫾2.4
Men
70–120
Women
55–100
Serum PTH, pmol/L
ⱖ50 y
Serum calcium, mmol/L
Serum 25-hydroxyvitamin D3, nmol/L
Intake of calcium, mg/d
High*
䡠䡠䡠
Serum creatinine, ␮mol/L
⬍50 y
Normal
33/31
1.1–6.8
1.1–7.5
2.20–2.60
2.29⫾0.10
2.24⫾0.09†
30–110
55.6⫾20.7
50.0⫾15.3
䡠䡠䡠
592.1⫾459.6
400.3⫾227.3†
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Intake of vitamin D, ␮g/d
䡠䡠䡠
9.2⫾6.4
7.8⫾5.7
BMI, kg/m2
䡠䡠䡠
25.7⫾3.8
27.5⫾4.4
Systolic BP, mm Hg
䡠䡠䡠
143.4⫾19.9
153.9⫾27.1‡
䡠䡠䡠
84.3⫾10.4
89.7⫾14.1‡
䡠䡠䡠
66.2⫾19.4
67.5⫾20.2
4.7⫾1.1
Diastolic BP, mm Hg
BMC, g
Lumbar spine
Femoral neck
䡠䡠䡠
4.7⫾1.1
Ward’s triangle
䡠䡠䡠
2.4⫾0.8
2.4⫾0.8
Trochanter
䡠䡠䡠
11.6⫾3.8
12.1⫾4.0
BMD, g/cm2
Lumbar spine
䡠䡠䡠
1.089⫾0.203
1.087⫾0.205
Femoral neck
䡠䡠䡠
0.862⫾0.151
0.855⫾0.133
Ward’s triangle
䡠䡠䡠
0.713⫾0.154
0.705⫾0.139
Trochanter
䡠䡠䡠
0.833⫾0.163
0.836⫾0.158
Values are mean⫾SD.
*Subjects with hyperparathyroidism were excluded.
†P⬍0.01 vs those with normal serum PTH; ‡P⬍0.05 vs those with normal serum PTH.
at all 4 places of measurement (standardized ␤ coefficients
from 0.44 to 0.59). None of the other variables reached
statistical significance in this respect. However, when those
with elevated serum PTH levels on both occasions (and thus
those with presumably the most profound calcium intake
deficit) were considered separately from those with persistently normal serum PTH levels, the BMC at the lumbar spine
was significantly reduced (64.5⫾17.2 versus 67.4⫾18.4 g,
P⬍0.02), as was the BMD at the lumbar spine and trochanter
(1.065⫾0.190 versus 1.099⫾0.203 g/cm2 and 0.816⫾0.149
versus 0.837⫾0.159 g/cm2, respectively; P⬍0.05).
BMC at the lumbar spine and the trochanter for these 2
PTH subgroups is shown stratified for BMI quartiles in
Figure 2.
Discussion
In the present study, 68% of those with an elevated serum
PTH level in 1995 had an increased PTH level when
reexamined 3 years later. Because the blood samples were not
drawn with subjects in the fasting state, the PTH secretion
may have been affected by the mineral content in food
recently ingested. This may partly explain why an initially
elevated PTH level was found normalized in some of the
subjects.
As could be expected, some of those with elevated serum
PTH levels at the follow-up were found to have hyperparathyroidism. However, the lack of other obvious causes for the
increased serum PTH levels, like diseases associated with
malabsorption, was remarkable.
From studies on selected subjects, vitamin D deficiency
and a significant inverse relation between serum 25hydroxyvitamin D and PTH have frequently been found in
the elderly.2,3 However, in the present study, there was no
significant difference in serum level or intake of vitamin D
between those with high or normal serum PTH levels.
Therefore, lack of vitamin D can hardly be the main explanation for the increased serum PTH levels in the present
study, even though the average vitamin D intake was slightly
below the recommendation of 10 ␮g (400 IU) per day for
those aged 51 to 70 years and 15 ␮g (600 IU) per day for
those aged ⱖ71 years.12
On the other hand, the serum calcium level and the intake
of calcium were remarkably low in the group with high serum
PTH. Admittedly, the food questionnaire used by us cannot
Jorde et al
TABLE 2.
Low Calcium Intake, High Serum PTH, and BP
1157
BP in Men and Women With Normal and High Serum PTH in 1998
PTH in Men in 1998
Variables
All subjects, N
Age, y
Systolic BP, mm Hg
PTH in Women in 1998
Normal
High
Normal
High
46
33
54
31
67.2⫾9.9
68.8⫾11.6
70.3⫾4.6
72.3⫾5.2
145.6⫾20.7
150.0⫾26.5
141.5⫾19.2
158.0⫾27.5*
Diastolic BP, mm Hg
86.3⫾11.9
88.9⫾14.7
82.6⫾8.6
90.5⫾13.6†
BMI, kg/m2
25.5⫾3.3
26.9⫾3.5
25.9⫾4.2
28.3⫾5.1†
PTH, pmol/L
Calcium intake, mg/d
Subjects without BP medication, n
4.5⫾1.2
8.9⫾2.3
4.6⫾1.2
9.3⫾2.6
503.0⫾501.8
393.7⫾251.7
661.0⫾416.0
407.4⫾202.2*
31
26
41
65.4⫾11.3
65.5⫾12.5
70.1⫾4.5
72.8⫾4.9
Systolic BP, mm Hg
141.3⫾19.1
152.6⫾26.2
142.1⫾19.8
164.4⫾28.3*
Diastolic BP, mm Hg
85.1⫾11.9
91.2⫾13.6
83.1⫾8.4
92.7⫾14.3*
BMI, kg/m2
25.6⫾3.6
27.1⫾3.4
24.9⫾3.9
26.6⫾4.3
PTH, pmol/L
4.6⫾1.2
8.6⫾2.4
4.5⫾1.3
9.2⫾2.3
584.3⫾607.6
396.9⫾268.6
706.9⫾454.3
442.8⫾217.6†
Age, y
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Calcium intake, mg/d
22
Values are mean⫾SD.
*P⬍0.01 vs those with normal serum PTH; †P⬍0.05 vs those with normal serum PTH.
there was a strong negative association between intake of
calcium and serum PTH.
However, it must be emphasized that in spite of the
difference in calcium intake, there was a considerable overlap
between the 2 groups. Thus, in addition to the low calcium
intake, additional individual factors must also be present,
such as a slightly reduced ability to absorb calcium or an
increased calcium excretion, possibly because of reduced
vitamin D sensitivity.
measure calcium intake as accurately as a dietary interview.
However, the questionnaire did include all dairy products,
which in a Norwegian diet are the main calcium sources.
Furthermore, the calcium intake was much lower than that
found in the control group and also much lower than that
recommended.13 This difference in calcium intake is the most
likely explanation for the low serum calcium levels and the
compensatory increased serum PTH. The multiple linear
regression analysis supports this view, in view of the fact that
TABLE 3.
Standardized Regression Coefficient ␤ and t Values From Linear Regression Model
Dependent Variables
Serum PTH*
Independent Variables
Systolic BP†
␤
t
␤
t
⫺0.114
⫺0.886
0.231
1.732
Diastolic BP‡
␤
t
Men
Age, y
BMI, kg/m
2
Intake of calcium, mg/d
Intake of vitamin D, ␮g/d
Calcium, mmol/L
25-Hydroxyvitamin D3, nmol/L
0.140
1.035
0.170
1.266
0.120
0.859
0.087
0.615
⫺0.145
⫺1.189
0.045
0.353
0.039
0.302
0.070
0.584
0.073
0.599
0.146
1.166
⫺0.240
⫺1.940
0.204
1.606
0.112
0.860
0.036
0.265
PTH, pmol/L
0.072
0.521
0.066
0.468
0.174
1.378
0.167
1.297
0.098
0.909
⫺0.117
⫺1.077
Women
Age, y
0.171
1.663
0.101
0.958
0.078
0.715
⫺0.011
⫺0.101
Intake of calcium, mg/d
⫺0.349
⫺3.376
0.123
1.074
0.167
1.443
Intake of vitamin D, ␮g/d
⫺0.171
⫺1.673
0.164
1.472
0.161
1.500
Calcium, mmol/L
⫺0.168
⫺1.693
0.100
0.957
⫺0.003
⫺0.029
25-Hydroxyvitamin D3, nmol/L
⫺0.159
⫺1.514
0.006
0.056
⫺0.059
⫺0.536
0.491
4.152
0.545
4.565
BMI, kg/m
2
PTH, pmol/L
Values of ⱍtⱍ ⬎1.96, ⱍtⱍ ⬎2.58, and ⱍtⱍ ⬎3.29 correspond to P⬍0.05, P⬍0.01, and P⬍0.001, respectively.
*R2⫽0.154 and 0.288, †R2⫽0.124 and 0.262, and ‡R⫽0.089 and 0.247 for males and females, respectively.
1158
Hypertension
May 2000
TABLE 4. BP, BMI, Serum PTH, and Calcium Intake in Women According to Serum PTH
Status in 1995 and 1998
Normal PTH in 1998
Variables
n
Normal PTH in 1995
High PTH in 1995
39
Age, y
Systolic BP, mm Hg
High PTH in 1998
Normal PTH in 1995
High PTH in 1995
15
6
25
71.3⫾4.0
67.5⫾5.0
75.2⫾6.3
71.6⫾4.8
140.1⫾20.2*
145.4⫾15.8
149.0⫾41.7
160.2⫾23.6
Diastolic BP, mm Hg
81.6⫾8.4†
85.3⫾9.1‡
81.5⫾16.2‡
92.6⫾12.3
BMI, kg/m2
25.5⫾3.7*
26.8⫾5.2
28.0⫾3.8
28.3⫾5.4
PTH, pmol/L
Calcium intake, mg/d
4.3⫾1.2
5.3⫾1.1
7.9⫾0.6
9.7⫾2.8
681.9⫾411.6*
607.9⫾436.8
504.5⫾181.7
383.1⫾203.2
Values are mean⫾SD.
*P⬍0.01, †P⬍0.001, and ‡P⬍0.05 vs those with high serum PTH in both 1995 and 1998.
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One would expect to see the most apparent effects of a low
calcium intake on the skeleton. Thus, a markedly reduced
calcium intake could lead to a negative calcium balance,14
loss of calcium from the skeleton, and the development of
osteoporosis. This was also found in the present study but
only when those with persistently elevated PTH levels were
compared with those with persistently normal serum PTH
levels. Those with persistently elevated serum PTH were
those with the lowest calcium intake and, presumably, those
with the most profound calcium deficit. Because BMC and
BMD increase with increasing BMI and because BMI was
considerable higher in those with elevated PTH levels, the
difference between the 2 groups was more evident when
stratified for BMI.
However, the most interesting observation in the present
study was the large difference in BP between females with
high and normal serum PTH levels. The difference was
⬇20 mm Hg for systolic BP and 10 mm Hg for diastolic BP
and was even larger after excluding those on medication for
Figure 1. Relation between mean systolic and diastolic BP and
BMI quartiles in women with normal serum PTH levels in 1998
(n⫽54, F) and in those with high serum PTH levels in 1998
(n⫽31, E). Error bars represent SEM. BMI quartiles (1 to 4) represent BMI ⱕ23.0, 23.1 to 25.7, 25.8 to 28.6, and ⬎28.6 kg/m2,
respectively.
hypertension. In spite of this large difference in BP, it was
somewhat surprising that only slightly more subjects with
high serum PTH levels were on BP medication compared
with those with normal serum PTH levels. As shown in the
stratified analysis, the difference in BP could not be ascribed
to differences in BMI values, which were higher in the group
with elevated serum PTH. Furthermore, in the multiple linear
regression analysis, serum PTH in women was strongly
associated with both systolic and diastolic BPs. Finally, the
most elevated BPs were seen in those with persistently
elevated serum PTH, a subgroup that also had the highest
serum PTH levels as well as the lowest calcium intake.
Although an association between BP and serum levels of
PTH has been described before,5,6,8 those studies were not
population-based and did not find the gender difference that
we observed. On the contrary, in the study by Young et al,7
males but not females with hypertension had elevated PTH
levels. This is hard to reconcile with the present findings and
is most likely the result of different study populations.
Figure 2. Relation between mean BMC measured at the lumbar
spine and at the trochanter and BMI quartiles in subjects with
normal serum PTH in both 1995 and 1998 (n⫽74, F) and in
those with high serum PTH levels in both 1995 and 1998 (n⫽48,
E). Error bars represent SEM. BMI quartiles (1 to 4) represent
BMI ⱕ23.0, 23.1 to 25.7, 25.8 to 28.6, and ⬎28.6 kg/m2,
respectively.
Jorde et al
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For a long time, there has been a discussion of whether a
reduced intake of calcium is associated with hypertension.15–17 This has been demonstrated in several18 –20 but not
all epidemiological studies,21 and the effect in intervention
studies has been marginal.22 In this respect, our group with
persistently elevated serum PTH is unique, because it represents subjects who most likely have been on a very lowcalcium diet for a number of years. Although the group
obviously is a selected one, it still represents a significant
proportion of the hypertensive population. Thus, of the
original 1113 subjects examined in 1995, 15.9% had a
systolic BP ⬎160 mm Hg, and of these, 16.9% had a PTH
level ⬎6.9 pmol/L.
In addition to throwing light on pathophysiological relations that otherwise would not be evident, this group would
also be ideal for testing whether an adequate calcium intake
is of importance for maintaining a normal BP. If that is the
case, the effect of calcium supplementation in this group
should be profound.
We cannot say whether the effect on the BP was caused by
the high PTH level or by the reduced calcium intake. This is
also difficult to determine because the 2 events are physiologically linked together, with minor changes in serum
calcium eliciting large changes in serum PTH.23 Furthermore,
an association is, of course, no proof of a causal relation, and
we cannot rule out that the high BP in the females and the low
BMC and BMD in those with persistently elevated serum
PTH levels were caused by factors not measured by us. One
possible candidate in this respect could be parathyroid hypertensive factor.24 Parathyroid hypertensive factor is suppressed
by high dietary calcium intake, and parathyroid hypertensive
factor–like activity levels have been found to be elevated in
hypertensive individuals.24,25
In spite of the above uncertainty, we find it fair to conclude
that if an elevated serum PTH level is found in an otherwise
healthy female and the serum calcium is not above or in the
upper normal range, one likely explanation could be a
reduced calcium intake. A controlled clinical trial to see
whether calcium supplementation will reduce the BP in a
group of patients with elevated PTH levels is clearly
indicated.
Acknowledgments
This study was supported by a grant from the Norwegian Research
Council and the University Hospital of Tromsø. The assistance by
the staff, and Annika Gustafsson in particular, at the Clinical
Research Unit at the University Hospital of Tromsø is
gratefully acknowledged.
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Relation Between Low Calcium Intake, Parathyroid Hormone, and Blood Pressure
Rolf Jorde, Johan Sundsfjord, Egil Haug and Kaare H. Bønaa
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Hypertension. 2000;35:1154-1159
doi: 10.1161/01.HYP.35.5.1154
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