Hypertension (HTN) affects an estimated 60 million Americans, and is a major cause of morbidity and mortality. Diet, circulating molecules, and the interaction between genetics and environment may all impact the risk of developing HTN. Using prospective study designs (cohort and nested case-control studies), we propose to examine novel risk factors for incident HTN in three large independent cohorts. Based upon data that folate, other B vitamins, and methionine can influence endothelial function either directly or through effects on circulating homocysteine (Hey), we hypothesize that higher intakes of folate, vitamin B6, and vitamin B12 will reduce the risk of incident HTN, while higher methionine intake will increase the risk. Furthermore, we propose that higher circulating levels of Hey and soluble intercellular adhesion molecule-1 (sICAM) increase the risk of HTN. Given data demonstrating effects of vitamin D metabolites on the renin angiotensin system, we also propose that higher vitamin D levels will be associated with a lower risk of HTN. Finally, we hypothesize that genetic polymorphisms in MTHFR and eNOS will significantly modify the relation between folate and vitamin B12 and the risk of incident HTN, and that polymorphisms in the vitamin D receptor (VDR) will modify the association between vitamin D levels and HTN.
The specific aims of this proposal are: (1) to assess the relation between novel and modifiable dietary factors and incident HTN;(2) to assess the relation between plasma levels of Hey, sICAM, and vitamin D metabolites and the subsequent development of HTN;and (3) to assess the interaction between MTHFR, eNOS, and VDR polymorphisms and specific environmental factors as they influence the risk of incident HTN. The candidate for this K08 award is John P. Forman, M.D., an Instructor in Medicine at Harvard Medical School, attending nephrologist at Brigham and Women's Hospital, and a Masters'Candidate in Epidemiology at Harvard School of Public Health. He is seeking further training and experience in advanced epidemiologic methods under the guidance of Gary C. Curhan, M.D., Sc.D., a well-known epidemiologist with an interest in HTN. This project proposal will provide the foundation for the candidate's future career as an independent and successful clinical scientist in HTN research.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL079929-05
Application #
7876736
Study Section
Special Emphasis Panel (ZHL1-CSR-O (M1))
Program Officer
Ni, Hanyu
Project Start
2006-09-15
Project End
2010-12-31
Budget Start
2010-07-01
Budget End
2010-12-31
Support Year
5
Fiscal Year
2010
Total Cost
$134,730
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Cohen, Lisa; Curhan, Gary C; Forman, John P (2012) Influence of age on the association between lifestyle factors and risk of hypertension. J Am Soc Hypertens 6:284-90
Vaidya, Anand; Williams, Jonathan S; Forman, John P (2012) The independent association between 25-hydroxyvitamin D and adiponectin and its relation with BMI in two large cohorts: the NHS and the HPFS. Obesity (Silver Spring) 20:186-91
Vaidya, A; Forman, J P; Williams, J S (2011) Vitamin D and the vascular sensitivity to angiotensin II in obese Caucasians with hypertension. J Hum Hypertens 25:672-8
Vaidya, Anand; Forman, John P; Hopkins, Paul N et al. (2011) 25-Hydroxyvitamin D is associated with plasma renin activity and the pressor response to dietary sodium intake in Caucasians. J Renin Angiotensin Aldosterone Syst 12:311-9
Zhang, Luxia; Curhan, Gary C; Forman, John P (2011) Plasma insulin-like growth factor-1 level and risk of incident hypertension in nondiabetic women. J Hypertens 29:229-35
Vaidya, Anand; Sun, Bei; Forman, John P et al. (2011) The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians. Clin Endocrinol (Oxf) 74:783-90
Vaidya, Anand; Forman, John P; Underwood, Patricia C et al. (2011) The influence of body mass index and renin-angiotensin-aldosterone system activity on the relationship between 25-hydroxyvitamin D and adiponectin in Caucasian men. Eur J Endocrinol 164:995-1002
Zhang, Luxia; Curhan, Gary C; Hu, Frank B et al. (2011) Association between passive and active smoking and incident type 2 diabetes in women. Diabetes Care 34:892-7
Stuebe, Alison M; Schwarz, Eleanor B; Grewen, Karen et al. (2011) Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study. Am J Epidemiol 174:1147-58
Vaidya, Anand; Pojoga, Luminita; Underwood, Patricia C et al. (2011) The association of plasma resistin with dietary sodium manipulation, the renin-angiotensin-aldosterone system, and 25-hydroxyvitamin D3 in human hypertension. Clin Endocrinol (Oxf) 74:294-9

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