Serum 25-hydroxyvitamin D and parathyroid hormone levels ... - Nature

Journal of Human Hypertension (2012) 26, 20–27 & 2012 Macmillan Publishers Limited All rights reserved 0950-9240/12 www.nature.com/jhh

ORIGINAL ARTICLE

Serum 25-hydroxyvitamin D and parathyroid hormone levels in relation to blood pressure in a cross-sectional study in older Chinese men R Chan1, D Chan2, J Woo1, C Ohlsson3, D Mellstro¨m3, T Kwok1 and P Leung2 1

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, New Territories, Hong Kong SAR; 2Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, New Territories, Hong Kong SAR and 3Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine and Geriatrics, University of Gothenburg, Gothenburg, Sweden

Vitamin D status, parathyroid hormone (PTH) level and their associations with blood pressure in Chinese population are unknown. This study examined these associations in older Chinese men. Blood pressure, serum 25-hydroxyvitamin D (25OHD) and PTH was measured in 939 community-dwelling Chinese men aged 65 years and older. Linear regression analyses were performed with adjustments for age, body mass index, education, season of measurement, medication use, self-reported history of stroke and Parkinson’s disease, and other lifestyle factors. In either crude or adjusted models, serum 25OHD was not associated with blood pressure, whereas increasing PTH levels was associated with higher blood pressure. Men in the

highest quartile of serum PTH level had a mean difference of 3.4 mm Hg and 2.8 mm Hg higher in as systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively, than men in the lowest quartile of serum PTH level (Ptrend ¼ 0.019 for SBP and o0.001 for DBP). In conclusion, the findings support an association between serum PTH and blood pressure, but not for serum 25OHD in older Chinese men whose vitamin D status is optimal. The lack of association between serum 25OHD and blood pressure may possibly because of the relatively high serum 25OHD levels of the study sample. Journal of Human Hypertension (2012) 26, 20 – 27; doi:10.1038/jhh.2010.126; published online 20 January 2011

Keywords: 25-Hydroxyvitamin D; parathyroid hormone; blood pressure; Chinese

Introduction Hypertension is an important public health challenge worldwide because of its high prevalence as well as enormous burden on morbidity and mortality. Worldwide hypertension is estimated to cause 7 million premature deaths and is responsible for around 5% of the current global disease burden.1 Hypertension also poses a significant disease burden in Hong Kong, and its prevalence, rate of in-patient discharges and deaths and death rate attributed to hypertensive diseases increased sharply with age.2 Numerous studies have shown that lifestyle factors are contributory factors for blood pressure and the risk of hypertension.3,4 A diet high in sodium intake and low potassium, calcium and Correspondence: Dr R Chan, Department of Medicine and Therapeutics, 9/F Clinical Sciences Building, Prince of Wales Hospital, Shatin, New Territories 852, Hong Kong SAR. E-mail: [email protected] Received 19 August 2010; revised 26 November 2010; accepted 5 December 2010; published online 20 January 2011

magnesium intake is associated with a higher blood pressure.5–8 Physical inactivity is also a risk factor for coronary heart disease in the elderly, through predisposition to the development of hypertension.9 Vitamin D deficiency is now recognised as a serious public health problem worldwide.10–12 Previous studies also showed that vitamin D deficiency was common in Hong Kong. In a study describing the vitamin D status of women of child-bearing age in Hong Kong and Beijing, vitamin D deficiency (p25 nmol l1) was found in 40% of Beijing and 18% of Hong Kong women, and over 90% of women in both cities were insufficient (p50 nmol l1).13 In another study, the impact of vitamin D insufficiency on risk of low bone mass, falls and osteoporotic fractures in 382 community dwelling Chinese adults over 50 years in Hong Kong was examined.14 The study showed that vitamin D insufficiency was common, and male sex, instead of female sex was also associated with low serum 25-hydroxyvitamin D (25OHD) levels in this community sample. A telephone interview survey of 547 middle-aged and

Vitamin D, parathyroid hormone and blood pressure R Chan et al 21

elderly Chinese women living in Hong Kong also showed that 62.3% women actively avoided sunlight exposure by staying indoors or using sunscreen products and parasols.15 In recent years, there is increasing evidence to support an association between vitamin D status and blood pressure.10 Scragg et al. reported an inverse association between serum 25OHD and blood pressure in the cross-sectional analysis, using data from 12 644 people aged X20 years without use of hypertensive medication in the Third US National Health and Nutrition Examination Survey.16 Jorde et al., in the Tromsø Study, further confirmed this cross-sectional association, but failed to find a relation between change in serum 25OHD levels and change in blood pressure nor that serum 25OHD levels predict future hypertension.17 An association between poor vitamin D status and blood pressure or hypertension could potentially be mediated by elevated parathyroid hormone (PTH) levels.18,19 Increased PTH level was associated with elevated blood pressure and hypertension in several studies.20,21 However, most studies were conducted on Western populations. Little is known of Chinese populations whose dietary habits and lifestyle differ from those of Western populations. The objective of this study was to examine the association between serum 25OHD or PTH, and blood pressure in Chinese men aged 65 or over in Hong Kong.

Methods Study population

Participants were from the Mr Os Hong Kong cohort,22 which was part of an international study of Osteoporotic Fractures in Men (Mr Os) also carried out in the United States23 and Sweden.24 A total of 2000 Chinese men aged 65 years or over living in the community were recruited in a health survey between 2001 and 2003. They were invited to the study centre for a comprehensive health check, by placing recruitment notices in community centers for the older people and housing estates. Several talks were also given at these centers explaining the purpose, procedures and investigations to be carried out. The inclusion criteria were that all participants should be able to walk or take public transport to the study site at the University teaching hospital in Shatin. Subjects who had bilateral hip replacements and who could not walk independently were excluded. As there was neither census listing nor general practice register for random population sampling in Hong Kong, subjects were recruited on voluntary basis and recruitment was stopped once the target sample size was reached. The aim was to recruit a stratified sample so that approximately 33% would be in each of these age groups: 65–69, 70–74, 75 þ . Compared with the general population in this age group, participants had higher educational level (12–18 vs 3–9% with tertiary education

in the age groups 80 þ , 75–79,70–74 and 65–69 years).25 This study was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong. Written informed consent was obtained from all subjects. A total of 2000 men were recruited and interviewed at baseline. A random subpopulation consisting of 988 men had fasting venous sampling for assay of serum 25OHD and PTH. Among these 988 men, data from 49 men were excluded in this paper because of the supplemental use of multivitamins containing vitamin D or an extreme value of serum 25OHD or PTH level. This paper therefore presented data from 939 men (47% of the original cohort). The questionnaire

Information was collected regarding age, education, smoking habit, alcohol use, self-reported history of stroke and Parkinson’s disease, physical activity and dietary intake. Information on the duration and level of past and current use of cigarettes, cigars and pipes was obtained. Smoking history was classified in terms of former smoking (at least 100 cigarettes smoked in a lifetime), current smoking and never smoking. For alcohol consumption, subjects were asked to report their daily frequency of intake of alcohol and other beverages in portion sizes specified on the semi-quantitative food frequency questionnaire. They were also asked to report on how many days of the week they consumed alcohol. Drinking status was defined as never, former or current drinker. Current drinkers were defined as those who drank at least 12 drinks of beer, wine (including Chinese wine) or liquor over the previous 12 months. Self-reported medical history was obtained at baseline on the basis of the subjects’ report of their physician’s diagnoses, supplemented by the identification of drugs brought to the interviewers. Physical activity level was assessed using the Physical Activity Scale of the Elderly (PASE).26 This is a 12-item scale measuring the average number of hours per day spent in leisure, household and occupational physical activities over the previous 7-days period. Activity weights for each item were determined on the basis of the amount of energy spent, and each item score was calculated by multiplying the activity weight with daily activity frequency. A summary score of all the items reflects the daily physical activity level. Dietary intake was assessed at baseline using a semi-quantitative food frequency questionnaire, and mean nutrient quantitation per day was calculated using food tables derived from McCance and Widdowson,27 and the Chinese Medical Sciences Institute.28 The food frequency questionnaire had been validated with the basal metabolic rate calculation and the 24-h sodium/creatinine and potassium/ creatinine analysis.29 The food frequency questionnaire consisted of 280 food items from seven Journal of Human Hypertension


categories of food groups; Bread/pasta/rice; vegetables; fruits; meat/fish/eggs; beverages; dimsum/ snacks; soups; and oil/salt/sauces. Each subject was asked to complete the questionnaire—the food item, the size of each portion, the number of times of consumption each day and each week. Portion size was explained to subjects using a catalogue of pictures of individual food portions. The amount of cooking oil was estimated according to the method of preparing different foods. For food items consumed less than once per week, information was obtained for consumption pattern over 1 year and the quantitation per day or week adjusted accordingly. Measurement of blood pressure

Blood pressure was measured after 5 min rest in the sitting position using a standard mercury sphygmomanometer (WA Baum Co. Inc., Copiague, NY, USA) by trained staff. The first and fifth Korotkoff phases were recorded as SBP (SBP) and diastolic blood pressure (DBP). The average of two readings was taken. Hypertension was defined as SBP X140 mm Hg and/or DBP X90 mm Hg, and/or use of anti-hypertensive medication.30 Anti-hypertension medication included in this study were diuretics, beta blockers, angiotensin converting enzyme inhibitors, angiotensin receptor antagonist, calcium channel blockers and alpha blockers. To obtain information on medication use, the participants had to show all the drugs he/she used at the moment of the medical interview at the study centre. The names, types and doses were noted by the interviewer. Physical measurements

Body weight was measured, with subjects wearing a light gown, by the Physician Balance Beam Scale (Healthometer, Alsip, IL, USA). Height was measured by the Holtain Harpenden stadiometer (Holtain Ltd, Crosswell, UK). Body mass index (BMI) was calculated as (body weight in kg per (height in m)2). Serum analyses of 25OHD and PTH

Fasting venous samples were collected at baseline for assay of serum 25OHD and PTH. Serum was stored at 80 1C and levels of 25OHD were measured by a competitive radioimmunoassay (DiaSorin, Stillwater, MN, USA). This assay measures both 25OHD3 and 25OHD2. Intraassay and interassay CVs were 6 and 18%, respectively. Serum levels of intact PTH were measured by an immunoluminometric assay (Diagnostic Products Corp., Los Angeles, CA, USA). Intraassay and interassay CVs were 5 and 9%, respectively. Statistical analysis

All statistical analyses were performed using the statistical package SPSS version 16.0 (SPSS Inc., Chicago IL, USA). Data was checked for normality Journal of Human Hypertension

by descriptive analysis and data transformation was applied for skewed data. Student’s t-test and the w2-test were used to test for differences in mean age, BMI, Physical Activity Scale of the Elderly, dietary intake of sodium, potassium, calcium, magnesium, and also differences in distribution of education level, smoking status, alcohol use, use of antihypertensive medication, and self-reported history of stroke and Parkinson’s disease between participants with blood measurement and participants without blood measurement. Serum 25OHD and PTH levels were stratified into quartiles for analyses. Differences across serum 25OHD and PTH quartiles were calculated by w2-test for categorical variables and by analysis of variance with P for trend or nonparametric Krusal– Wallis test for continuous variables. Analysis of covariance was applied to examine the association between quartiles of serum 25OHD or PTH level and SBP or DBP. Multivariate models were adjusted for potential confounding factors, including age (years), BMI (kg m2), Physical Activity Scale of the Elderly, education level (primary or below, secondary or matriculation, University or above), smoking status (never smoker vs ex- or current smoker), alcohol use (yes vs no), dietary intake of calcium, sodium, potassium, magnesium and season of serum 25OHD measurement (spring and winter vs summer and autumn), use of antihypertensive medications (yes vs no) and self-reported history of stroke (yes vs no) and Parkinson’s disease (yes vs no). An a level of 5% was used as the level of significance.

Results There were no significant differences in education level, smoking status, alcohol use, daily intake of calcium, sodium, magnesium and potassium from diet, use of anti-hypertensive medications, and selfreported history of stroke and Parkinson’s disease between men with (n ¼ 988) and without (n ¼ 1 012) assay of serum 25OHD and PTH. However, men with assay of serum 25OHD and PTH were older, more likely to exercise and had lower BMI (Po0.05) (data not shown). Characteristics of 939 men in the final sample are shown in Table 1 and Table 2. Mean (s.d.) age of the sample was 72.8(5.1) years. Mean (s.d.) serum 25OHD level and median (interquartile range) serum PTH level was 77.9(20.5) nmol l1 and 4.1(3.1–5.5) pmol l1, respectively. There were 55(5.9%), 390(41.5%) and 494(52.6%) men being classified as deficient insufficient (50–74.9 nmol l1) (o50 nmol l1), 1 and sufficient (X75 nmol l ) 25OHD status. A large proportion of our sample had hypertension (74.3%). Men in the highest quartile of serum 25OHD level were likely to have lower BMI, lower dietary sodium intake and serum 25OHD measurement not in winter and spring (Table 1). Men in the lowest quartile of serum PTH level were likely to have


Table 1 Baseline subject characteristics by quartiles of serum 25OHD Serum 25OHD (nmol l1)

Variable 1st p63 (n ¼ 239) Mean (n) (s.d. (%)) Serum 25OHD concentration (nmol l1) Serum PTH concentration (pmol l1)b Age (years) BMI (kg m2) PASE score Dietary intake (mg per day) Calcium Potassium Sodium Magnesium

2nd 463– o76 (n ¼ 252) Mean (n) (s.d. (%))

3rd 476–o91 (n ¼ 221) Mean (n) (s.d. (%))

Pa 4th 491 (n ¼ 227) Mean (n) (s.d (/%))

54.4 4.7 72.5 23.5 101.7

(7.0) (3.6–6.1) (5.2) (3.3) (60.8)

69.9 4.1 73.1 23.0 94.6

(4.1) (3.1–5.6) (5.3) (2.9) (46.5)

83.5 4.1 72.6 23.3 99.0

(4.4) (2.9–5.0) (4.6) (3.2) (50.3)

106.1 3.7 72.9 22.7 102.8

(13.1) (2.7–4.9) (5.1) (3.0) (55.3)

— o0.001 0.628 0.022 0.623

626.9 3212.5 1800.7 376.8

(306.6) (1165.6) (846.2) (166.6)

611.2 3202.6 1678.3 373.7

(283.4) (1173.0) (903.6) (164.9)

622.4 3171.1 1662.9 396.6

(280.2) (1289.4) (869.4) (208.1)

610.1 3294.0 1622.1 380.5

(273.3) (1218.1) (758.1) (181.4)

0.639 0.548 0.027 0.519

Education level (%) Primary or below Secondary/matriculation University or above

126 (52.7) 70 (29.3) 43 (25.4)

148 (58.7) 76 (30.2) 28 (11.1)

127 (57.5) 60 (27.1) 34 (15.4)

147 (64.8) 57 (25.1) 23 (10.1)

0.080

Smoking status (%) Never smoke Ex-or current Smoker

206 (86.2) 33 (13.8)

219 (86.9) 33 (13.1)

197 (89.1) 24 (10.9)

200 (88.1) 27 (11.9)

0.783

Alcohol use (%) No Yes

176 (73.6) 63 (26.4)

189 (75.0) 63 (25.0)

175 (79.2) 46 (20.8)

177 (78.0) 50 (22.0)

0.468

Season of measurement (%) Winter and spring (low vitamin D season) Summer and autumn (high vitamin D season) Use of anti-hypertensive medications (%)

133 (55.6) 106 (44.4) 99 (41.4)

116 (46.0) 136 (54.0) 116 (46.0)

98 (44.3) 123 (55.7) 106 (48.0)

82 (36.1) 145 (63.9) 110 (48.5)

o0.001

Self-reported history (%) Stroke Parkinson’s disease Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)

9 0 140.9 77.7

(3.8) (0.0) (20.0) (10.0)

11 3 143.2 78.9

(4.4) (1.2) (19.4) (8.4)

17 3 141.0 78.0

(7.7) (1.4) (20.5) (9.6)

18 2 143.0 78.2

(7.9) (0.9) (19.7) (9.3)

0.406 0.110 0.382 0.484 0.772

a

Differences between groups were assessed by w2-test and analysis of variance, the significant P values are in bold. Median (interquartile range), group difference was assessed by Krusal–Wallis test.

b

higher dietary magnesium intake (Table 2). No significant differences in other lifestyle factors, use of anti-hypertensive drugs, and self-reported history of stroke and Parkinson’s disease among the four quartiles of serum 25OHD or PTH were observed. Serum 25OHD was not associated with either SBP or DBP in crude model or in adjusted models (Table 3). In contrast, higher serum PTH level was statistically associated with higher SBP and DBP, and this association remained statistically significant after controlling for other confounders. Men in the highest quartile of serum PTH level had a mean difference of 3.4 and 2.8 mm Hg higher in SBP and DBP, respectively, than men in the lowest quartile of serum PTH level (Ptrend ¼ 0.019 for SBP and o0.001 for DBP) (Table 3). A stronger association between serum PTH level and SBP or DBP was observed when subjects using anti-hypertensive medication were excluded (Table 4).

Discussion In this cross-sectional study of 939 communitydwelling older men, vitamin D status was not significantly associated with blood pressure, whereas increasing PTH levels was associated with higher SBP and DBP. These findings are supported by results of some observational studies,31,32 but not the others.16,21,33 In the Longitudinal Ageing Study Amsterdam, serum PTH rather than serum 25OHD was associated with SBP or DBP, or prevalence of hypertension in 1205 men and women aged 65 years and older after adjustment of potential confounders.31 The result was consistent with that of the Ranch Bernardo Study. In the Ranch Bernardo Study with 1070 men and women with mean age of 74.5 years, serum 25OHD was not associated with prevalence of hypertension in both sexes, whereas increasing level of PTH was significantly associated Journal of Human Hypertension


Table 2 Baseline subject characteristics by quartiles of serum PTH Serum PTH (nmol l1)

Variable 1st o ¼ 3.1 (n ¼ 248) Mean (n) (s.d. (%)) Serum PTH concentration (pmol l1) Serum 25OHD concentration (nmol l1) Age (years) BMI (kg m2) PASE score Dietary intake (mg per day) Calcium Potassium Sodium Magnesium

2.6 83.9 72.3 23.2 97.0 647.6 3286.4 1734.3 398.5

(2.1–2.8)b (20.8) (4.9) (2.8) (51.1) (286.4) (1169.3) (901.5) (94.3)

2nd 3.2 to 4.1 (n ¼ 232) Mean (n) (s.d. (%)) 3.7 78.5 72.9 23.1 102.7

(304–3.9) (21.0) (4.9) (3.2) (54.4)

612.5 3217.1 1645.1 392.0

(299.1) (1289.7) (854.0) (189.8)

3rd 4.2 to 5.5 (n ¼ 223) Mean (n) (s.d. (%))

Pa 4th 45.5 (n ¼ 230) Mean (n) (s.d. (%))

4.8 77.0 73.1 23.2 97.2

(4.4–5.1) (19.3) (5.2) (3.3) (55.9)

6.7 71.5 72.8 23.1 100.3

(6.0–7.9) (19.0) (5.2) (3.3) (51.3)

— o0.001 0.215 0.674 0.774

588.8 3188.6 1691.6 359.4

(269.4) (1235.0) (848.7) (164.5)

622.8 3183.4 1700.1 373.4

(286.3) (1092.30) (787.4) (162.8)

0.237 0.333 0.821 0.038

Education level (%) Primary or below Secondary/matriculation University or above

144 (58.1) 76 (30.6) 28 (11.3)

135 (58.20) 60 (25.90) 37 (15.90

132 (59.2) 66 (29.6) 25 (11.2)

134 (58.3) 58 (25.2) 38 (16.5)

0.410

Smoking status (%) Never smoke Ex-or current smoker

215 (86.7) 33 (13.3)

202 (87.10 30 (12.9)

193 (86.5) 30 (3.5)

206 (89.6) 24 (10.4)

0.738

Alcohol use (%) No Yes

178 (71.8) 70 (28.2)

186 (80.2) 46 (19.8)

175 (78.5) 48 (21.5)

172 (74.8) 58 (25.2)

0.133

Season of measurement (%) Winter and spring (low vitamin D season) Summer and autumn (high vitamin D season) Use of anti-hypertensive medications (%)

112 (45.2) 136 (54.8) 117

109 (47.0) 123 (53.0) 98 (42.2)

105 (47.1) 118 (52.9) 101 (45.3)

99 (43.0) 131 (57.0) 114 (49.60)

0.801

Self-reported history (%) Stroke Parkinson’s disease Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)

15 2 140.1 76.8

(6.0) (0.8) (18.4) (8.8)

12 2 140.5 77.6

(5.2) (0.9) (20.4) (9.6)

12 4 144.1 79.2

(5.4) (1.8) (20.3) (9.4)

15 0 143.5 79.3

(6.5) (0.0) (20.2) (9.3)

0.444 0.922 0.015 0.001

a

Differences between groups were assessed by w2-test and analysis of variance, the significant P values are in bold. Median (interquartile range).

b

with higher prevalence of hypertension in men but not in women in the adjusted models.32 In contrast, results of the National Health and Nutrition Examination Survey (2003–2006) with large sample size have shown that both serum concentrations of 25OHD and PTH were independently associated with blood pressure and with the presence of hypertension or prehypertension among the United States adults.21 Many studies have also reported that PTH levels are associated with increased blood pressure34,35 and a higher risk of hypertension.20 Although we did not find any association between serum 25OHD and blood pressure, previous crosssectional studies16,33 have documented an inverse relationship between serum 25OHD and blood pressure. In the cross-sectional analyses restricted to 12 644 people aged 20 years and above, mean (standard error) SBP was 3.0 (0.7) mm Hg lower (P ¼ 0.0004) and DBP was 1.6 (0.6) mm Hg lower (P ¼ 0.011) for participants in the highest quintile Journal of Human Hypertension

(25OHDX85.7 nmol l1) compared with the lowest (25OHDo40.4 nmol l1), after adjustment for age, sex, ethnicity and physical activity.16 Evidence from prospective studies, however, are limited and mixed. One study reported no association between serum 25OHD and future hypertension or change in blood pressure,17 whereas other studies demonstrated a positive association between plasma 25OHD and risk of developing hypertension.36,37 The lack of association between vitamin D status and blood pressure might be attributable to the relatively high baseline levels of serum 25OHD among the participants in these studies, as in our study.18 To our knowledge, only one study has been conducted to examine the association between plasma 25OHD and blood pressure in Chinese.38 In the study by Lu et al., the main objective was to examine the cross-sectional association of plasma 25OHD with metabolic syndrome in 1443 men


Table 3 Adjusted mean (s.e.)d of SBP and DBP by quartiles of serum 25OHD and PTH concentration (n ¼ 939) Quartiles

SBP (mm Hg)

DBP (mm Hg)

Model 1a

Model 2b

Model 3c

Crude

Model 1a

Model 2b

Model 3c

Serum 25OHD (nmol l1) Q1 (o ¼ 63) 140.9 (1.3) Q2 (463–o ¼ 76) 143.2 (1.3) Q3 (476–o ¼ 91) 141.0 (1.3) Q4 (491) 143.0 (1.3) 0.484 Ptrendd

140.8 (1.6) 144.3 (1.6) 142.0 (1.7) 144.7 (1.7) 0.124

141.3 (1.6) 144.7 (1.7) 142.3 (1.7) 144.9 (1.7) 0.168

133.7 (4.0) 137.2 (4.0) 134.7 (4.0) 137.2 (4.0) 0.187

77.7 (0.6) 78.9 (0.6) 78.0 (0.6) 78.2 (0.6) 0.772

77.0 (0.7) 79.2 (0.7) 78.1 (0.8) 78.7 (0.8) 0.152

77.0 (0.7) 79.2 (0.7) 78.1 (0.8) 78.7 (0.8) 0.147

72.1 (1.9) 74.4 (1.8) 73.3 (1.8) 73.9 (1.8) 0.120

Serum PTH (pmol l1) Q1 (o ¼ 3.1) Q2 (3.2–4.1) Q3 (4.2–5.5) Q4 (45.5) Ptrendd

140.9 (1.6) 141.4 (1.6) 144.9 (1.6) 144.6 (1.6) 0.013

141.2 (1.6) 141.9 (1.6) 145.3 (1.6) 144.8 (1.6) 0.016

133.6 (4.0) 134.3 (4.0) 137.9 (3.9) 137.0 (4.0) 0.019

76.8 (0.6) 77.6 (0.6) 79.2 (0.6) 79.3 (0.6) 0.001

76.7 (0.7) 77.6 (0.7) 79.3 (0.7) 79.5 (0.8) o0.001

76.7 (0.7) 77.5 (0.7) 79.2 (0.8) 79.5 (0.8) o0.001

71.9 (1.8) 72.7 (1.8) 74.5 (1.8) 74.7 (1.9) o0.001

Crude

140.1 (1.3) 140.5 (1.3) 144.1 (1.3) 143.5 (1.3) 0.015

a Adjusted for age, BMI, education, PASE, smoking status, alcohol use, season of measurement, dietary intake of sodium, potassium, calcium and magnesium. b Further adjusted for anti-hypertensive medication use. c Further adjusted for self-reported history of stroke and Parkinson’s disease. d By analysis of covariance with serum 25OHD and PTH concentration included simultaneously in all crude and adjusted models.

Table 4 Adjusted mean (s.e.)c of SBP and DBP by quartiles of serum 25OHD and PTH concentration in subjects without use of anti-hypertensive medications (n ¼ 508) Quartiles

SBP (mm Hg)

DBP (mm Hg)

Crude

Model 1a

Model 2b

Crude

Model 1a

Model 2b

Serum 25OHD (nmol l1) Q1 (o ¼ 63) Q2 (463 to o ¼ 76) Q3 (476 to o ¼ 91) Q4 (491) Ptrendc

139.9 (1.6) 141.3 (1.6) 138.1 (1.8) 140.7 (1.8) 0.935

138.2 (1.9) 141.3 (2.0) 138.7 (2.1) 142.1 (2.1) 0.244

134.5 (5.7) 137.7 (5.7) 135.2 (5.6) 138.6 (5.8) 0.228

78.1 (0.8) 78.5 (0.8) 77.5 (0.8) 78.4 (0.8) 0.982

76.5 (0.9) 78.1 (0.9) 77.0 (1.0) 78.1 (1.0) 0.309

69.9 (2.6) 71.7 (2.6) 70.6 (2.6) 71.6 (2.7) 0.295

Serum PTH (pmol l1) Q1 (o ¼ 3.1) Q2 (3.2 to 4.1) Q3 (4.2 to 5.5) Q4 (45.5) Ptrendc

135.8 (1.7) 139.9 (1.6) 141.4 (1.7) 143.6 (1.8) 0.001

135.4 (2.0) 139.7 (2.0) 141.5 (2.0) 143.7 (2.1) 0.001

131.9 (5.6) 136.1 (5.8) 138.0 (5.6) 140.1 (5.8) 0.001

76.5 (0.8) 78.5 (0.8) 77.7 (0.8) 79.9 (0.8) 0.011

75.5 (0.9) 77.7 (0.9) 77.3 (1.0) 79.3 (1.0) 0.004

69.1 (2.6) 71.0 (2.7) 70.9 (2.6) 72.7 (2.7) 0.004

a Adjusted for age, BMI, education, PASE, smoking status, alcohol use, season of measurement, dietary intake of sodium, potassium, calcium and magnesium. b Further adjusted for self-reported history of stroke and Parkinson’s disease. c By analysis of covariance with serum 25OHD and PTH concentration included simultaneously in all crude and adjusted models.

and 1819 women aged 50–70 years from Beijing and Shanghai in China. An inverse association between plasma 25OHD and DBP, but not SBP in both simple and adjusted analyses was observed. The result was different from that of ours. We speculated that the difference in vitamin D status between the two studies was the main reason to explain the conflicting results. In Lu’s study, the mean of plasma 25OHD was 40.4 nmol l1 and the percentage of vitamin D deficiency was 69.2%. In our study, the mean serum 25OHD level was 77.9 nmol l1 and only 5.9% of subjects was vitamin D deficient. The high mean 25OHD levels and low prevalence of vitamin D deficiency may lessen the chances of detecting an inverse association between serum 25OHD and blood pressure in our study.

Several mechanisms may help explain the relationships among vitamin D, PTH and blood pressure.18 The renin–angiotensin–aldosterone system has a central role in the regulation of blood pressure and electrolyte, and volume homeostasis. Vitamin D has been shown to suppress renin–angiotensin–aldosterone system by inactivating renin gene expression and inhibiting renin synthesis.39 Other antihypertensive effects of vitamin D include renoprotective effects, vasodilatatory and antiatherosclerotic properties, and effects on calcium homeostasis including prevention of secondary hyperparathyroidism.18,40,41 In contrast, PTH has been shown to stimulate renin release by activation of the renin–angiotensin– aldosterone system.18 Additionally, PTH may affect blood pressure by its direct effects on arteries and Journal of Human Hypertension


myocytes to promote arterial stiffness and left ventricular hypertrophy, respectively.42 Strength of our study includes adjustment for several potential confounders, including dietary intake of nutrients relevant to blood pressure. However, our study had several limitations. First, our study is cross-sectional in nature, which precludes establishing causal relationships between serum concentrations of 25OHD and PTH, and blood pressure or hypertension. Second, our study consisted of moderate sample size of about 1000 men, which decreased the probability of detecting a significant association between serum 25OHD and blood pressure. Third, the high mean 25OHD levels (77.9 nmol l1) indicated that this sample would have few men with very low serum 25OHD levels, which may lessen the chances of detecting an inverse association between serum 25OHD and blood pressure. Furthermore, we did not collect information on medical history of chronic kidney disease, which has been suggested as one of the important confounders.43 Another limitation was the use of a single measurement of serum 25OHD and PTH. It can be questioned whether serum 25OHD and PTH level measured at a single point in time reflects only recent exposure rather than long-term exposure. Moreover, our sample as a whole was of a higher educational standard compared with the general Hong Kong population, and there were slight differences in some demographic and lifestyle characteristics between those with and without serum assays. In addition, the subjects were neither selected randomly from the general population nor recruited from a welldefined population. Therefore, the results may not be generalised to the general population. In conclusion, this study shows that vitamin D status is not associated with blood pressure, whereas increasing PTH levels is associated with higher blood pressure in a sample of communitydwelling Chinese older men that vitamin D deficiency is not common. Future prospective studies and controlled trials should evaluate the role of serum 25OHD and PTH as determinants of blood pressure in populations with higher prevalence of vitamin D deficiency. What is known about the topic K Accumulating evidence to support an association between poor vitamin D status and elevated blood pressure, and this association may be mediated by increased parathyroid hormone level. K Most studies are conducted with Western populations and limited data on Chinese populations. What this study adds K The study findings confirmed that an elevated level of serum parathyroid hormone was associated with higher systolic blood pressure and diastolic blood pressure. K The study results did not support an association between vitamin D status and blood pressure, possibly because of the relatively optimal vitamin D status of this sample of Chinese older men.

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Conflict of interest The authors declare no conflict of interest.

Acknowledgements We would like to thank Ms Kay Yuen for coordination of this study. This study was supported by grants from the Research Grants Council of Hong Kong, CUHK 4101/02M; the Hong Kong Jockey Club Charities Trust; the SH Ho Centre for Gerontology and Geriatric, and the Centre for Nutritional Studies, The Chinese University of Hong Kong.

References 1 Whitworth JA. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003; 21: 1983–1992. 2 Centre for Health Protection of the Department of Health. Hypertension: The silent killer. Non-communicable Diseases Watch. Centre for Health Protection of the Department of Health: Hong Kong SAR, 2010. 3 Woo J. Relationships among diet, physical activity and other lifestyle factors and debilitating diseases in the elderly. Eur J Clin Nutr 2000; 54: S143–S147. 4 Woo J, Ho SC, Yu AL. Lifestyle factors and health outcomes in elderly Hong Kong Chinese aged 70 years and over. Gerontology 2002; 48: 234–240. 5 Kwok TC, Chan TY, Woo J. Relationship of urinary sodium/potassium excretion and calcium intake to blood pressure and prevalence of hypertension among older Chinese vegetarians. Eur J Clin Nutr 2003; 57: 299–304. 6 Miura K, Okuda N, Turin TC, Takashima N, Nakagawa H, Nakamura K et al. Dietary salt intake and blood pressure in a representative Japanese population: baseline analyses of NIPPON DATA80. J Epidemiol 2010; 20: S524–S530. 7 Anonymous. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 h urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ 1988; 297: 319–328. 8 Cappuccio FP, Elliott P, Allender PS, Pryer J, Follman DA, Cutler JA. Epidemiologic association between dietary calcium intake and blood pressure: a meta-analysis of published data. Am J Epidemiol 1995; 142: 935–945. 9 Bijnen FC, Caspersen CJ, Mosterd WL. Physical inactivity as a risk factor for coronary heart disease: a WHO and International Society and Federation of Cardiology position statement. Bull World Health Organ 1994; 72: 1–4. 10 Martini LA, Wood RJ. Vitamin D and blood pressure connection: update on epidemiologic, clinical, and mechanistic evidence. Nutr Rev 2008; 66: 291–297. 11 Harris S. Emerging roles of vitamin D: More reasons to address widespread vitamin D insufficiency. Mol Aspects Med 2008; 29: 359–360. 12 Lim SK, Kung AW, Sompongse S, Soontrapa S, Tsai KS. Vitamin D inadequacy in postmenopausal women in Eastern Asia. Curr Med Res Opin 2008; 24: 99–106. 13 Woo J, Lam CW, Leung J, Lau WY, Lau E, Ling X et al. Very high rates of vitamin D insufficiency in women of


14 15

16

17

18 19 20 21

22

23

24

25

26 27 28 29

child-bearing age living in Beijing and Hong Kong. Br J Nutr 2008; 99: 1330–1334. Wat WZ, Leung JY, Tam S, Kung AW. Prevalence and impact of vitamin D insufficiency in southern Chinese adults. Ann Nutr Metab 2007; 51: 59–64. Kung AW, Lee KK. Knowledge of vitamin D and perceptions and attitudes toward sunlight among Chinese middle-aged and elderly women: a population survey in Hong Kong. BMC Public Health 2006; 6: 226. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens 2007; 20: 713–719. Jorde R, Figenschau Y, Emaus N, Hutchinson M, Grimnes G. Serum 25-hydroxyvitamin D levels are strongly related to systolic blood pressure but do not predict future hypertension. Hypertension 2010; 55: 792–798. Pilz S, Tomaschitz A, Ritz E, Pieber TR. Vitamin D status and arterial hypertension: a systematic review. Nat Rev Cardiol 2009; 6: 621–630. 18. Nyirenda MJ, Padfield PL. Parathyroid hormone and hypertension. J Hypertens 2005; 23: 1633–1634. Taylor EN, Curhan GC, Forman JP. Parathyroid hormone and the risk of incident hypertension. J Hypertens 2008; 26: 1390–1394. Zhao G, Ford ES, Li C, Kris-Etherton PM, Etherton TD, Balluz LS. Independent associations of serum concentrations of 25-hydroxyvitamin D and parathyroid hormone with blood pressure among US adults. J Hypertens 2010; 28: 1821–1828. Lau EM, Leung PC, Kwok T, Woo J, Lynn H, Orwoll E et al. The determinants of bone mineral density in Chinese men—results from Mr. Os (Hong Kong), the first cohort study on osteoporosis in Asian men. Osteoporos Int 2006; 17(2): 297–303. Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K et al. Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study—a large observational study of the determinants of fracture in older men. Contemp Clin Trials 2005; 26: 569–585. Ribom EL, Grundberg E, Mallmin H, Ohlsson C, Lorenzon M, Orwoll E et al. Estimation of physical performance and measurements of habitual physical activity may capture men with high risk to fall—data from the Mr Os Sweden cohort. Arch Gerontol Geriatr 2009; 49: e72–e76. Census and Statistics Department. Hong Kong 2006 Population By-Census Thematic Report: Older PersonsimP. Census and Statistics Department: Hong Kong SAR, 2006. Washburn RA, Smith KW, Jette AM, Janney CA. The physical activity scale for the elderly (PASE): development and evaluation. J Clin Epidemiol 1993; 46: 153–162. Paul AA. The Composition of Foods. HMSO: London, 1978. Yang Y, Wang G, Pan X. China Food Compositon 2002. University Medical Press: Peking, 2002. Woo J, Leung SSF, Ho SC, Lam TH, Janus ED. A food frequency questionnaire for use in the Chinese

30

31

32

33

34 35 36

37

38

39

40

41

42 43

population in Hong Kong: Description and examination of validity. Nutr Res 1997; 17: 1633–1641. Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001–2004). Am J Cardiol 2008; 102: 1540–1544. Snijder MB, Lips P, Seidell JC, Visser M, Deeg DJ, Dekker JM et al. Vitamin D status and parathyroid hormone levels in relation to blood pressure: a population-based study in older men and women. J Intern Med 2007; 261: 558–565. Reis JP, von Muhlen D, Kritz-Silverstein D, Wingard DL, Barrett-Connor E. Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care 2007; 30: 1549–1555. Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2007; 167: 1159–1165. Jorde R, Sundsfjord J, Haug E, Bonaa KH. Relation between low calcium intake, parathyroid hormone, and blood pressure. Hypertension 2000; 35: 1154–1159. Jorde R, Svartberg J, Sundsfjord J. Serum parathyroid hormone as a predictor of increase in systolic blood pressure in men. J Hypertens 2005; 23: 1639–1644. Forman JP, Curhan GC, Taylor EN. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension 2008; 52: 828–832. Forman JP, Giovannucci E, Holmes MD, BischoffFerrari HA, Tworoger SS, Willett WC et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 2007; 49: 1063–1069. Lu L, Yu Z, Pan A, Hu FB, Franco OH, Li H et al. Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals. Diabetes Care 2009; 32(7): 1278–1283. Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Bio 2004; 89-90: 387–392. Wakasugi M, Noguchi T, Inoue M, Kazama Y, Tawata M, Kanemaru Y et al. Vitamin D3 stimulates the production of prostacyclin by vascular smooth muscle cells. Prostaglandins 1991; 42: 127–136. Kahonen M, Nappi S, Jolma P, Hutri-Kahonen N, Tolvanen JP, Saha H et al. Vascular influences of calcium supplementation and vitamin D-induced hypercalcemia in NaCl-hypertensive rats. J Cardiovasc Pharmacol 2003; 42: 319–328. Fitzpatrick LA, Bilezikian JP, Silverberg SJ. Parathyroid hormone and the cardiovascular system. Curr Osteoporos Rep 2004; 6: 77–83. Levin A, Li YC. Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease? Kidney Int 2005; 68: 1973–1981.

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