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Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

BMJ 2003; 326 doi: (Published 19 April 2003) Cite this as: BMJ 2003;326:845

Rapid Response:

A hypertensive pregnancy can warn of inflammatory disease later in life

The steroid hormone 1,25-dihydroxyvitamin-D is elevated in pregnancy,
so hypertensive disease during pregnancy can be a warning of inflammatory disease later in life

I am not surprised by the association between hypertensive pregnancy disorders
and hypertension/stroke reported by
Wilson, et al [1]. We have observed that the genetic
abnormalities pre-disposing to Th1 inflammation [2] also cause the Blood Pressure
(BP) to become positively related to the concentration of the steroid
hormone 1,25-dihydroxyvitamin-D (1,25-D). In 'controls' the
association is negative - BP usually goes down as 1,25-D

During pregnancy an excess of this steroid hormone is manufactured by the
placenta, most probably to activate the immune system and protect the fetus
from infection [6]. In patients predisposed to dysregulation of 1,25-D
synthesis, the placental generation of excess 1,25-D hormone will lead to a concurrent increase in BP.

Abnormalities of the 1,25-D metabolism have been associated with a
number of diseases, including Rheumatic disease and Cardiac
disease [7]. We have shown that this steroid hormone, and
the corticosteroid Angiotensin II, are both key factors in the biochemistry of the body's Th1
inflammatory response [8].

Using our 'D-Ratio' technique [8], we have analysed the raw data collected
by Vieth, et al [9] from a cohort of 1710 Canadian euthyroid patients.
Our analysis shows a high incidence of occult 1,25-D metabolic
dysfunction. This
agrees with our own data, and suggests maybe 3-10% of the population could
have some degree of 1,25-D dysfunction, with the consequent risk of inflammatory disease.

I would urge the authors to carefully study the concentration of this
steroid hormone. It held the key to the etiology of Sarcoid
Inflammation [8], and I believe it also holds the key to the link
between pregnancy, hypertension, and the inflammation leading to circulatory
disease. This Th1 biochemistry explains why Angiotensin Receptor Antagonists offer
protection against both immune disease [8],
cardiovascular complications, and stroke [10].

1. Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM,
Hannaford P, Smith WCS: Hypertensive diseases of pregnancy and risk of
hypertension and stroke in later life: results from cohort study
2003; 326:845 [Publisher Full Text]

2. Marshall TG: Brown, et al, ACCESS Study finds Bacterial Pathogens in Sarcoidosis
. [Electronic Letter]
Chest 6 Feb 2003;
Available from URL,
Accessed 12 Feb 2003

3. Li YC: Vitamin D regulation of the renin-angiotensin system. J
Cell Biochem 2003;88(2):327-31 [Pubmed Abstract]

4. Basile JN, Liel Y, Shary J, Bell NH: Increased calcium intake does
not suppress circulating 1,25-dihydroxyvitamin D in normocalcemic patients
with sarcoidosis.
J Clin Invest 1993 Apr;91(4):1396-8 [PubMed Abstract]

5. Kristal-Boneh E, Froom P, Harari G, Ribak J: Association of
Calcitriol and Blood Pressure in Normotensive Men.
1997;30:1289-1294 [Publisher Full Text]

6. Zehnder D, Evans KN, Kilby MD, Bulmer JN, Innes BA, Stewart PM,
Hewison M: The ontogeny of 25-hydroxyvitamin D(3) 1alpha-hydroxylase
expression in human placenta and decidua.
Am J Pathol 2002
Jul;161(1):105-14 [Pubmed Abstract]

7. Marshall TG, Marshall FE: Vitamin D may be Harmful in Rheumatic
. BMJ Rapid Response 13 Jan 2003 [Full Text]

8. Marshall TG, Marshall FE: The Science Points to Angiotensin II and
1,25-Dihydroxyvitamin D.
[Electronic Letter]
Chest 6 Feb 2003;
Available from URL,
Accessed 27 Mar 2003

9. Vieth R, Ladak Y, Walfish PG: Age-related changes in the
25-hydroxyvitamin D versus parathyroid hormone relationship suggest a
different reason why older adults require more vitamin D.
J Clin
Endocrinol Metab 2003 Jan;88(1):185-91 [Pubmed Abstract]

10. Droste DW, Ritter MA, Dittrich R, Heidenreich S, Wichter T, Freund M,
Ringelstein EB: Arterial hypertension and ischaemic stroke. Acta
Neurol Scand 2003; 107(4):241-251 
PubMed Abstract]

Competing interests:  
None declared

Competing interests: No competing interests

19 April 2003
Trevor G Marshall
Research Director
Sarcinfo, Thousand Oaks, California 91360