A Biomarker to Detect Salt Sensitivity

Natriuretic peptides (NPs) are molecules that regulate blood pressure by inducing natriuresis and vasodilation. We have shown that higher baseline levels of NT-proBNP are associated with the development of hypertension and humans elevated NT-proBNP levels demonstrate resistance to the action of NPs and are unable to handle high dietary sodium loads. These findings have led us to propose that pre-hypertensive or newly diagnose hypertensive individuals, free of overt cardiovascular disease, who have elevated levels of NT-proBNP will experience a substantial rise in total body water and arterial blood pressure when exposed to a high sodium load. If this hypothesis holds true, then NT-proBNP could be used as a biological marker to identify salt sensitivity and for the prescription of low sodium diets to hypertensive individuals. Research design: Individuals with physiological levels of NT-proBNP (40 - 90 pg/mL) and those with elevated levels (\> 120 pg/mL) will be recruited to participate in a randomized crossover feeding study designed to treat patients with hypertension. A total of 8 participants, per group, will be exposed to two 10 days-phases of either a low sodium load (LS) of 50 mmol/day or a high sodium load (HS) of 250 mmol/day in random order and compare the blood pressure response to different sodium loads between the two NT-proBNP categories. Salt sensitivity is defined as a change in mean arterial blood pressure of ≥ 10% between the low and high sodium load. At the end of each phase, participants will be tested on a variety of anthropometric, blood and urinary measurements. Variables measured: Total body water will be determined using bioelectrical impedance from Valhalla Scientific body comp scale®. Blood pressure monitors will be provided to each participant for measurement and record their own blood pressure twice daily for the duration of the study. In addition, at the end of each of the two sodium loading phases, trained personnel will measure BP three time using standard procedures, following an 8 hour fast and a 10 minute rest period at the clinic. Laboratory measurements. Blood and urine analysis will be performed at the start and end of each salt loading phase at the Advanced Research and Diagnostic Laboratory (ARDL). NT-proBNP will be measured using the Roche-Elecsys proBNP® (Roche Diagnostics, Indianapolis, IN). This method has a range of values that extends from 1 - 25000 pg/mL and the intra-assay precision is below 4% and the CV and interassay precision below 5% 21. Plasma BNP will be measured on a Siemens Advia Centaur instrument using a chemiluminescent immunoassay which has a minimal detection limit of 1.9 pg/mL and a CV of 3.4%. cGMP will be measured using a competitive enzyme immunoassay by Bio-Techne (Minneapolis, MN) intra essay CV is 7%. NT-proBNP will be measured using the Roche-Elecsys proBNP® (Roche Diagnostics, Indianapolis, IN). This method has a range of values that extends from 1 - 25000 pg/mL and the intra-assay precision is below 4% CV and inter-assay precision below 5% 21. Anticipated results and future studies. Individuals with elevated NT-proBNP will have a significant increase in mean blood pressure and total body water (salt sensitive individuals) and a greater BNP/cGMP ratio when compared to those with physiological levels of NT-proBNP. Power analysis shows that for a randomized cross-over study we would need 25 individuals per group for a 90% power.