Sodium Sensitivity, Sodium Resistance, and Incidence of Hypertension

Cross-sectional studies have reported that high sodium sensitivity is more common among individuals with hypertension. Experimental studies have also reported various animal models with sodium-resistant hypertension. It is unknown, however, whether sodium sensitivity and resistance precede the development of hypertension. We conducted a feeding study, including a 7-day low-sodium diet (1180 mg/day) followed by a 7-day high-sodium diet (7081 mg/day), among 1718 Chinese adults with blood pressure (BP) <140/90 mm Hg. We longitudinally followed them over an average of 7.4 years. Three BP measurements and 24-hour urinary sodium excretion were obtained on each of 3 days during baseline observation, low-sodium and high-sodium interventions, and 2 follow-up studies. Three trajectories of BP responses to dietary sodium intake were identified using latent trajectory analysis. Mean (SD) changes in systolic BP were −13.7 (5.5), −4.9 (3.0), and 2.4 (3.0) mm Hg during the low-sodium intervention and 11.2 (5.3), 4.4 (4.1), and −0.2 (4.1) mm Hg during the high-sodium intervention ( P <0.001 for group differences) in high sodium-sensitive, moderate sodium-sensitive, and sodium-resistant groups, respectively. Compared with individuals with moderate sodium sensitivity, multiple-adjusted odds ratios (95% CIs) for incident hypertension were 1.43 (1.03–1.98) for those with high sodium sensitivity and 1.43 (1.03–1.99) for those with sodium resistance ( P =0.006 for nonlinear trend). Furthermore, a J-shaped association between systolic BP responses to sodium intake and incident hypertension was identified ( P <0.001). Similar results were observed for diastolic BP. Our study indicates that individuals with either high sodium sensitivity or sodium resistance are at an increased risk for developing hypertension.

Thiazide-Sensitive NCC (Sodium-Chloride Cotransporter) in Human Metabolic Syndrome

The thiazide-sensitive sodium-chloride cotransporter (NCC;SLC12A3) is central to sodium and blood pressure regulation. Metabolic syndrome induces NCC upregulation generating sodium-sensitive hypertension in experimental animal models. We tested the role of NCC in sodium sensitivity in hypertensive humans with metabolic syndrome. Conversely, oral potassium induces NCC downregulation producing potassium-induced natriuresis. We determined the time course and magnitude of potassium-induced natriuresis compared with the natriuresis following hydrochlorothiazide (HCTZ) as a reference standard. We studied 19 obese hypertensive humans with metabolic syndrome during 13-day inpatient confinement. We determined sodium sensitivity by change in 24-hour mean systolic pressure by automated monitor from days 5 (low sodium) to 10 (high sodium). We determined NCC activity by standard 50 mg HCTZ sensitivity test (day 11). We determined potassium-induced natriuresis following 35 mmol KCl (day 13). We determined (1) whether NCC activity was greater in sodium-sensitive versus sodium-resistant participants and correlated with sodium sensitivity and (2) time course and magnitude of potassium-induced natriuresis following 35 mmol KCl directly compared with 50 mg HCTZ. NCC activity was not greater in sodium-sensitive versus sodium-resistant humans and did not correlate with sodium sensitivity. Thirty-five-millimoles KCl produced a rapid natriuresis approximately half that of 50 mg HCTZ with a greater kaliuresis. Our investigation tested a key hypothesis regarding NCC activity in human hypertension and characterized potassium-induced natriuresis following 35 mmol KCl compared with 50 mg HCTZ. In obese hypertensive adults with metabolic syndrome ingesting a high-sodium diet, 35 mmol KCl had a net natriuretic effect approximately half that of 50 mg HCTZ.

Abstract 55: Sodium Sensitivity, Sodium Resistance, and Incidence of Hypertension

Background: Blood pressure responses to dietary sodium intake vary among individuals. However, it is unknown whether sodium sensitivity and sodium resistance predict incidence of hypertension. Methods: We conducted a feeding study, including a 7-day low-sodium diet (51.3 mmol/day) and a 7-day high-sodium diet (307.8 mmol/day), among 1,718 Chinese individuals with normal blood pressure in 2003-2005 and follow-up studies in 2008-2009 and 2011-2012. Three blood-pressure measurements and 24-hour urinary sodium excretion were obtained on each of 3 days during baseline, low- and high-sodium interventions, and follow-up visits. Latent class models were used to identify subgroups that share a similar underlying trajectory in blood-pressure responses to dietary sodium intake. Results: Three trajectories of systolic blood pressure responses to dietary sodium intake were identified (Figure). Mean (standard deviation) changes in systolic blood pressure were -13.7 (5.5), -4.9 (3.0), and 2.4 (3.0) mmHg during the low-sodium intervention, and 11.2 (5.3), 4.4 (4.1) and -0.2 (4.1) mmHg during the high-sodium intervention ( P< 0.001 for group differences) in high sodium-sensitive, moderate sodium-sensitive, and sodium-resistant groups, respectively. Compared to individuals with moderate sodium sensitivity, multiple-adjusted odds ratio (95% confidence intervals) for incident hypertension were 1.44 (1.03 to 1.99) for those with high sodium sensitivity and 1.42 (1.02 to 1.97) for those with sodium resistance ( P <0.001 for quadratic trend). Furthermore, a J-shaped association between systolic blood pressure responses to high sodium intake and incident hypertension was identified ( P <0.001). Similar results were observed for diastolic blood pressure. Conclusions: Individuals with either high sodium sensitivity or sodium resistance are at an increased risk for developing hypertension.

P1689Nighttime blood pressure and dipping patterns relate to sodium sensitivity of blood pressure

Background Attenuated nighttime blood pressure (BP) fall during a high-sodium diet is associated with higher sodium sensitivity of BP. However, the prognostic value for sodium sensitivity of nighttime BP profile during a habitual diet is not fully understood. Purpose To elucidate the usefulness of nighttime BP and dipping patterns under a habitual diet in assessing sodium sensitivity. Methods We conducted a dietary intervention study among 250 resident aged 18–60 years with high-normal or stage I hypertension in rural areas of northern China. The 24-hour ambulatory BP monitoring and baseline survey were performed for each participant under a habitual diet during the first 3 days. Then participants underwent a 7-day low-sodium intervention (51.3mmol sodium per day), followed by a 7-day high-sodium intervention (307.8mmol sodium per day). Three clinic BP measurements were obtained in every morning of the 3-day baseline observation and days 5, 6, and 7 of each intervention period. Results Among 250 participants, 86 (34.4%) had daytime hypertension (DH) and 149 (59.6%) had nighttime hypertension (NH). The systolic BP (SBP) responses to low-sodium and high-sodium intervention were significantly higher in those with NH than those without irrespective of DH status [−8.1 (−9.3, −7.0) vs. −5.5 (−7.0, −4.1) mmHg, P=0.001; and 13.0 (11.6, 14.3) vs. 11.0 (9.3, 12.7) mmHg, P=0.038, respectively]. Compared with dippers, extreme dippers had significantly higher SBP responses to low-sodium and high sodium intervention independently of 24-hour SBP. Moreover, the quadratic curve between nighttime SBP fall and SBP responses to low-sodium (β=−105.5 for quadratic term, P=0.015) and high-sodium (β=108.9 for quadratic term, P=0.035) intervention suggested both non-dipping and extreme dipping might indicate higher sodium sensitivity. Conclusions NH as well as non-dipping and extreme dipping determined during a habitual diet might indicate higher sodium sensitivity, which highlights the potential usefulness of nighttime BP profile in assessing sodium sensitivity. Acknowledgement/Funding This study is supported by the National Natural Science Foundation of China (grant no. 81570386)