Novel Risk Factors For Hypertension

Summary

Principal Investigator: John P Forman
Abstract: DESCRIPTION (provided by applicant): 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. (End of Abstract)
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Plasma 25-hydroxyvitamin D levels and risk of incident hypertension
    John P Forman
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Hypertension 49:1063-9. 2007
  2. pmc Influence of age on the association between lifestyle factors and risk of hypertension
    Lisa Cohen
    Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD, USA
    J Am Soc Hypertens 6:284-90. 2012
  3. pmc Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women
    John P Forman
    Department of Medicine, Renal Division and Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachussetts, USA
    Hypertension 52:828-32. 2008
  4. pmc Higher levels of albuminuria within the normal range predict incident hypertension
    John P Forman
    Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Soc Nephrol 19:1983-8. 2008
  5. ncbi Parathyroid hormone and the risk of incident hypertension
    Eric N Taylor
    Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Hypertens 26:1390-4. 2008
  6. ncbi Renin-angiotensin system polymorphisms and risk of hypertension: influence of environmental factors
    John P Forman
    Renal Division, The Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    J Clin Hypertens (Greenwich) 10:459-66. 2008
  7. ncbi Association between the serum anion gap and blood pressure among patients at Harvard Vanguard Medical Associates
    J P Forman
    J Hum Hypertens 22:122-5. 2008
  8. pmc Habitual intake of flavonoid subclasses and incident hypertension in adults
    Aedin Cassidy
    School of Medicine, University of East Anglia, Norwich, United Kingdom
    Am J Clin Nutr 93:338-47. 2011
  9. pmc Vitamin D and the vascular sensitivity to angiotensin II in obese Caucasians with hypertension
    A Vaidya
    Division of Endocrinology, Diabetes and Hypertension, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Hum Hypertens 25:672-8. 2011
  10. pmc 25-Hydroxyvitamin D is associated with plasma renin activity and the pressor response to dietary sodium intake in Caucasians
    Anand Vaidya
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital and Harvard Medical School, USA
    J Renin Angiotensin Aldosterone Syst 12:311-9. 2011

Scientific Experts

Detail Information

Publications27

  1. ncbi Plasma 25-hydroxyvitamin D levels and risk of incident hypertension
    John P Forman
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Hypertension 49:1063-9. 2007
    ..31 (95% CI: 2.03 to 2.63) in men and 1.57 (95% CI: 1.44 to 1.72) in women. Plasma 25(OH)D levels are inversely associated with risk of incident hypertension...
  2. pmc Influence of age on the association between lifestyle factors and risk of hypertension
    Lisa Cohen
    Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD, USA
    J Am Soc Hypertens 6:284-90. 2012
    ..We sought to determine whether the strength of traditional hypertensive risk factors varied with age...
  3. pmc Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women
    John P Forman
    Department of Medicine, Renal Division and Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachussetts, USA
    Hypertension 52:828-32. 2008
    ..7% of the study population) had a multivariable odds ratio of 1.47 (95% CI: 1.10 to 1.97). Plasma 25(OH)D levels are inversely and independently associated with the risk of developing hypertension...
  4. pmc Higher levels of albuminuria within the normal range predict incident hypertension
    John P Forman
    Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Soc Nephrol 19:1983-8. 2008
    ..The definition of normal albumin excretion should be reevaluated...
  5. ncbi Parathyroid hormone and the risk of incident hypertension
    Eric N Taylor
    Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Hypertens 26:1390-4. 2008
    ..We conducted a prospective study to examine the association between plasma intact parathyroid hormone levels and the subsequent risk of developing hypertension...
  6. ncbi Renin-angiotensin system polymorphisms and risk of hypertension: influence of environmental factors
    John P Forman
    Renal Division, The Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    J Clin Hypertens (Greenwich) 10:459-66. 2008
    ..These data suggest that demographic and dietary factors may influence the associations between RAS polymorphisms and hypertension and could explain heterogeneity in prior studies...
  7. ncbi Association between the serum anion gap and blood pressure among patients at Harvard Vanguard Medical Associates
    J P Forman
    J Hum Hypertens 22:122-5. 2008
    ..27 mm Hg (P=0.08) higher systolic, 0.20 mm Hg (P=0.05) higher diastolic and 0.22 mm Hg (P=0.04) higher mean arterial pressure; these results suggest that endogenous acid production may raise the risk of hypertension...
  8. pmc Habitual intake of flavonoid subclasses and incident hypertension in adults
    Aedin Cassidy
    School of Medicine, University of East Anglia, Norwich, United Kingdom
    Am J Clin Nutr 93:338-47. 2011
    ..Dietary flavonoids have beneficial effects on blood pressure in intervention settings, but there is limited information on habitual intake and risk of hypertension in population-based studies...
  9. pmc Vitamin D and the vascular sensitivity to angiotensin II in obese Caucasians with hypertension
    A Vaidya
    Division of Endocrinology, Diabetes and Hypertension, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Hum Hypertens 25:672-8. 2011
    ..Future studies to evaluate the effect of vitamin D supplementation on vascular RAS activity in obesity are needed...
  10. pmc 25-Hydroxyvitamin D is associated with plasma renin activity and the pressor response to dietary sodium intake in Caucasians
    Anand Vaidya
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital and Harvard Medical School, USA
    J Renin Angiotensin Aldosterone Syst 12:311-9. 2011
    ..We investigated the association between PRA and 25-hydroxyvitamin D (25OHD), the most clinically relevant vitamin D metabolite, and whether 25OHD associates with SS of BP in renin phenotypes of hypertension...
  11. pmc Association between passive and active smoking and incident type 2 diabetes in women
    Luxia Zhang
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Diabetes Care 34:892-7. 2011
    ..This analysis examined the association between exposure to passive smoke, active smoking, and the risk of incident type 2 diabetes among women...
  12. pmc The influence of body mass index and renin-angiotensin-aldosterone system activity on the relationship between 25-hydroxyvitamin D and adiponectin in Caucasian men
    Anand Vaidya
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital, 221 Longwood Avenue, RFB 386, Boston, Massachusetts 02115, USA
    Eur J Endocrinol 164:995-1002. 2011
    ..We evaluated the association between adiponectin and 25-hydroxyvitamin D (25(OH)D) after controlling RAAS activity with dietary sodium equilibration and also evaluated whether this relationship was influenced by BMI...
  13. pmc The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians
    Anand Vaidya
    Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Clin Endocrinol (Oxf) 74:783-90. 2011
    ....
  14. pmc The independent association between 25-hydroxyvitamin D and adiponectin and its relation with BMI in two large cohorts: the NHS and the HPFS
    Anand Vaidya
    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Obesity (Silver Spring) 20:186-91. 2012
    ..Since lower levels of 25(OH)D and adiponectin are associated with higher cardio-metabolic risk, assessing the effect of vitamin D supplementation on adiponectin levels is warranted...
  15. pmc Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study
    Alison M Stuebe
    Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Am J Epidemiol 174:1147-58. 2011
    ....
  16. pmc The association of plasma resistin with dietary sodium manipulation, the renin-angiotensin-aldosterone system, and 25-hydroxyvitamin D3 in human hypertension
    Anand Vaidya
    Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Clin Endocrinol (Oxf) 74:294-9. 2011
    ..Both resistin and vitamin D have been associated with the renin-angiotensin-aldosterone system (RAAS). We investigated the association between resistin and the RAAS, and resistin and vitamin D under controlled dietary sodium conditions...
  17. pmc Plasma insulin-like growth factor-1 level and risk of incident hypertension in nondiabetic women
    Luxia Zhang
    Channing Laboratory, Renal Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Hypertens 29:229-35. 2011
    ..Insulin-like growth factor-1 may be involved in regulation of blood pressure through multiple pathways; however, the prospective association between plasma insulin-like growth factor-1 level and risk of hypertension has never been explored...
  18. pmc Determinants of plasma parathyroid hormone levels in young women
    Julie M Paik
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 5th Floor, 181 Longwood Avenue, Boston, MA, 02115, USA
    Calcif Tissue Int 87:211-7. 2010
    ..Additional research is needed to elucidate the mechanisms whereby smoking, vitamin A, and phosphorus affect PTH and to examine how body size and season may affect PTH independent of 25(OH)D...
  19. pmc Fructose and vitamin C intake do not influence risk for developing hypertension
    John P Forman
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, 3rd Floor, 181 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Am Soc Nephrol 20:863-71. 2009
    ..02 (0.91 to 1.14) in Nurses' Health Study 2, and 1.06 (0.97 to 1.15) in Health Professionals Follow-up Study. In conclusion, fructose and vitamin C intake do not substantially influence the risk for developing hypertension...
  20. pmc Uric acid and insulin sensitivity and risk of incident hypertension
    John P Forman
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Arch Intern Med 169:155-62. 2009
    ..Corresponding circulating biomarkers are associated with risk of hypertension, but because these factors may be interrelated, whether they independently affect risk is unknown...
  21. pmc Diet and lifestyle risk factors associated with incident hypertension in women
    John P Forman
    Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    JAMA 302:401-11. 2009
    ..Hypertension is an important preventable risk factor for death among women. While several modifiable risk factors have been identified, their combined risk and distribution in the population have not been assessed...
  22. pmc Diet-dependent net acid load and risk of incident hypertension in United States women
    Luxia Zhang
    Channing Laboratory Renal Division, Brigham and Women s Hospital, 181 Longwood Ave, Boston, MA 02115, USA
    Hypertension 54:751-5. 2009
    ..In conclusion, a high diet-dependent net acid load is independently associated with a higher risk of incident hypertension...
  23. pmc Insulin resistance and risk of incident hypertension among men
    Tai Shuan Lai
    Renal Division, National Taiwan University Hospital, Yun Lin branch, Yun Lin, Taiwan
    J Clin Hypertens (Greenwich) 11:483-90. 2009
    ..93 (1.01-3.71) but was 0.67 (0.37-1.24) among older men. Insulin resistance is independently associated with incident hypertension among younger men...
  24. pmc Urinary melatonin and risk of incident hypertension among young women
    John P Forman
    Channing Laboratory, Department of Medicine, 181 Longwood Avenue, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Hypertens 28:446-51. 2010
    ..However, whether lower physiologic levels of melatonin are an independent risk factor for the development of hypertension has never been reported...
  25. pmc Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans
    John P Forman
    Renal Division and Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Hypertension 55:1283-8. 2010
    ..These data suggest that low plasma 25-hydroxyvitamin D levels may result in upregulation of the RAS in otherwise healthy humans...
  26. pmc Plasma prolactin level and risk of incident hypertension in postmenopausal women
    Luxia Zhang
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Hypertens 28:1400-5. 2010
    ..Laboratory and cross-sectional human studies suggest a potential role for prolactin in the pathogenesis of hypertension; however, the prospective association between prolactin and hypertension has not been previously reported...
  27. pmc Plasma resistin levels associate with risk for hypertension among nondiabetic women
    Luxia Zhang
    Channing Laboratory, Department of Medicine, Renal Division, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Soc Nephrol 21:1185-91. 2010
    ..In conclusion, higher plasma resistin levels independently associate with an increased risk for incident hypertension among women without diabetes...