The Systolic Blood Pressure Intervention Trial (SPRINT) affords a unique opportunity to determine if the difference in peripheral (brachial) systolic blood pressure (SBP) that will develop between the intensive treatment group (target SBP <120 mm Hg) and the usual care group (target SBP <140 mm Hg) will be accompanied by significant differences in measures of vascular stiffness (aortic pulse wave velocity, aPWV) and central (aortic) BP. The overall hypothesis addressed in this SPRINT ancillary study is that measures of vascular stiffness will be predictive of the main SPRINT outcomes independent of the achieved peripheral SBP. Three primary specific aims are proposed.
Specific Aim 1 : To determine if aPWV (and sub-aim 1, measures of central BP) in SPRINT study subjects randomized to the intensive treatment group at year three post-randomization will be lower compared to the usual care treatment group.
Specific Aim 2 : To determine if the aPWV (and sub-aim 2, measures of central BP) achieved (adjusted for baseline value) in SPRINT study subjects will be an independent predictor of the primary SPRINT outcomes (CV disease events) as well as all cause mortality, decline in renal function, rate of incident dementia and age-related cognitive decline.
Specific Aim 3 : To determine the associations at baseline between aPWV and central BP and relevant biomarkers of vascular aging and stiffness (fasting glucose, insulin, insulin sensitivity, hemoglobin A1C, and renin and aldosterone) and markers associated with chronic kidney disease (CKD - serum calcium, phosphorous, parathyroid hormone levels, uric acid and urinary albumin). This time-sensitive ancillary study to SPRINT will add important information regarding the underlying mechanisms for vascular stiffness by assessing clinically relevant biomarkers for glucose metabolism, insulin sensitivity, the renin-angiotensin-aldosterone system, and markers associated with CKD. In addition, by collecting baseline (at randomization) and longitudinal, annual measures of vascular stiffness (aPWV) and central aortic BP using a validated, reproducible, non-invasive methodology, the value of these measures with regard to the primary SPRINT clinical outcomes will be determined. No large scale studies have addressed whether reductions in vascular stiffness per se - independent of the fall in peripheral BP - provides a better predictor of clinical benefits. Moreover, no study has assessed the change in aPWV or central aortic BP in patients treated to a target SBP of 120 mm Hg. The addition of measures of vascular stiffness will help to determine if these outcomes should be considered as a therapeutic target over and above the peripheral BP achieved. The addition of aPWV and central aortic BP measures as well as several biomarkers of vascular stiffness in this SPRINT ancillary study are therefore important scientific additions to the parent trial.
Project Narrative The age-associated increase in blood pressure combined with the world-wide demographic increase in the aging population means that hypertension represents an enormous emerging global public health concern. Vascular stiffness that develops with aging is a major contributor to the development of hypertension. This ancillary study to the Systolic Blood Pressure Intervention Trial (SPRINT) study will investigate potentially useful clinical measures and surrogate biomarkers of vascular stiffness to determine if measures of vascular stiffness should be should be considered as a therapeutic target over and above the reduced peripheral systolic blood pressure that will be achieved in the intensive treatment arm of the SPRINT study.
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| Pajewski, Nicholas M; Williamson, Jeff D; Applegate, William B et al. (2016) Characterizing Frailty Status in the Systolic Blood Pressure Intervention Trial. J Gerontol A Biol Sci Med Sci 71:649-55 |
| Williamson, Jeff D; Supiano, Mark A; Applegate, William B et al. (2016) Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ?75 Years: A Randomized Clinical Trial. JAMA 315:2673-82 |
| Scialla, Julia J; Xie, Huiliang; Rahman, Mahboob et al. (2014) Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 25:349-60 |
| Wing, Maria R; Ramezani, Ali; Gill, Harindarpal S et al. (2013) Epigenetics of progression of chronic kidney disease: fact or fantasy? Semin Nephrol 33:363-74 |
