Higher aldosterone and lower N-terminal proatrial natriuretic peptide as biomarkers of salt sensitivity in the community.
ABSTRACT: Salt sensitivity, a trait characterized by a pressor blood pressure response to increased dietary salt intake, has been associated with higher rates of cardiovascular target organ damage and cardiovascular disease events. Recent experimental studies have highlighted the potential role of the natriuretic peptides and aldosterone in mediating salt sensitivity.Prospective cohort study.We evaluated 1575 non-hypertensive Framingham Offspring cohort participants (mean age 55?±?9 years, 58% women) who underwent routine measurements of circulating aldosterone and N-terminal proatrial natriuretic peptide (NT-ANP) and assessment of dietary sodium intake. Participants were categorized as potentially 'salt sensitive' if their serum aldosterone was >sex-specific median but plasma NT-ANP was ?sex-specific median value. Dietary sodium intake was categorized as lower versus higher (dichotomized at the sex-specific median). We used multivariable linear regression to relate presence of salt sensitivity (as defined above) to longitudinal changes (?) in systolic and diastolic blood pressure on follow-up (median four years).Participants who were 'salt sensitive' (N?=?437) experienced significantly greater increases in blood pressure (? systolic, +4.4 and +2.3?mmHg; ? diastolic, +1.9 and -0.3?mmHg; on a higher versus lower sodium diet, respectively) as compared to the other participants (? systolic, +2.8 and +1.0?mmHg; ? diastolic, +0.5 and -0.2?mmHg; on higher versus lower sodium diet, respectively; P?=?0.033 and P?=?0.0127 for differences between groups in ? systolic and ? diastolic blood pressure, respectively).Our observational data suggest that higher circulating aldosterone and lower NT-ANP concentrations may be markers of salt sensitivity in the community. Additional studies are warranted to confirm these observations.
Project description:At present, the effect of substitute salt in reducing sodium intake and blood pressure is relatively clear. The present study is a phase I clinical trial involving 43 hypertensives in which the effect of 18% sodium substitute salt on the home blood pressure variability (BPV) was observed for 8 weeks with weekly follow-up. Finally, 4 patients were lost, and 39 patients completed the intervention and were included in the analysis. Daily home blood pressure and weekly adverse events were collected. The systolic blood pressure (SBP) in the morning (-10.0 mmHg, 95% CI: -16.5 to -3.5, <i>P</i> = 0.003), SBP at night (-10.2 mmHg, 95% CI: -16.1 to -4.3, <i>P</i> = 0.001), and diastolic blood pressure (DBP) at night (-4.0 mmHg, 95% CI: -7.1 to -0.8, <i>P</i> = 0.014) decreased significantly. Also, there was no statistically significant change in morning (<i>F</i> = 1.137, <i>P</i> = 0.352) and night diastolic (<i>F</i> = 0.344, <i>P</i> = 0.481) BPV and morning systolic BPV (<i>F</i> = 0.663, <i>P</i> = 0.930) over time during the intervention period, except for that night systolic BPV had a downward trend (<i>F</i> = 2.778, <i>P</i> = 0.016) and had decreased 2.04 mmHg (95% CI: 0.84 to 3.23, <i>P</i> = 0.001) after intervention. The use of 18% of the substitute salt did not increase BPV during the intervention and even may decrease it, which indicates its control effects on blood pressure. This study is the first one to observe the effect of 18% sodium substitute salt on the home blood pressure variability, providing a basis for further experiments.
Project description:Each heart was assigned to one of the following three conditions: phasic systolic overload (SO), phasic diastolic overload (DO), and no loading throughout the cardiac cycle (control; CN). We created SO by isovolumic contraction (peak systolic LVP > 170 mmHg) at a constant diastolic volume with end-diastolic pressure (EDP) equals 0 mmHg. For DO, we increased LVV in diastole so that EDP reached 40 mmHg, and unloaded quickly in systole to minimize LVP generation. At the end of 3 hours, the myocardium from each heart was collected for subsequent analyses. rat heart subjected to phasic systolic overload and diastolic overload
Project description:Human alpha-1 antitrypsin (hAAT) is a versatile protease inhibitor, but little is known about its targets in the aldosterone-sensitive distal nephron and its role in electrolyte balance and blood pressure control. We analyzed urinary electrolytes, osmolality, and blood pressure from hAAT transgenic (hAAT-Tg) mice and C57B/6 wild-type control mice maintained on either a normal salt or high salt diet. Urinary sodium, potassium, and chloride concentrations as well as urinary osmolality were lower in hAAT-Tg mice maintained on a high salt diet during both the active and inactive cycles. hAAT-Tg mice showed a lower systolic blood pressure compared to C57B6 mice when maintained on a normal salt diet but this was not observed when they were maintained on a high salt diet. Cathepsin B protein activity was less in hAAT-Tg mice compared to wild-type controls. Protein expression of the alpha subunit of the sodium epithelial channel (ENaC) alpha was also reduced in the hAAT-Tg mice. Natriuretic peptide receptor C (NPRC) protein expression in membrane fractions of the kidney cortex was reduced while circulating levels of atrial natriuretic peptide (ANP) were greater in hAAT-Tg mice compared to wild-type controls. This study characterizes the electrolyte and blood pressure phenotype of hAAT-Tg mice during the inactive and active cycles and investigates the mechanism by which ENaC activation is inhibited in part by a mechanism involving decreased cathepsin B activity and increased ANP levels in the systemic circulation.
Project description:<h4>Objectives</h4>To evaluate the effects of a low-sodium and high-potassium salt-substitute on lowering blood pressure (BP) among Tibetans living at high altitude (4300 meters).<h4>Method</h4>The study was a patient-blinded randomized controlled trial conducted between February and May 2009 in Dangxiong County, Tibetan Autonomous Region, China. A total of 282 Tibetans aged 40 or older with known hypertension (systolic BP?140 mmHg) were recruited and randomized to intervention (salt-substitute, 65% sodium chloride, 25% potassium chloride and 10% magnesium sulfate) or control (100% sodium chloride) in a 1: 1 allocation ratio with three months' supply. Primary outcome was defined as the change in BP levels measured from baseline to followed-up with an automated sphygmomanometer. Per protocol (PP) and intention to treat (ITT) analyses were conducted.<h4>Results</h4>After the three months' intervention period, the net reduction in SBP/DBP in the intervention group in comparison to the control group was -8.2/-3.4 mmHg (all p<0.05) in PP analysis, after adjusting for baseline BP and other variables. ITT analysis showed the net reduction in SBP/DBP at -7.6/-3.5 mmHg with multiple imputations (all p<0.05). Furthermore, the whole distribution of blood pressure showed an overall decline in SBP/DBP and the proportion of patients with BP under control (SBP/DBP<140 mmHg) was significantly higher in salt-substitute group in comparison to the regular salt group (19.2% vs. 8.8%, p?=?0.027).<h4>Conclusion</h4>Low sodium high potassium salt-substitute is effective in lowering both systolic and diastolic blood pressure and offers a simple, low-cost approach for hypertension control among Tibetans in China.<h4>Trial registration</h4>ClinicalTrials.gov NCT01429246.
Project description:Many public health policies in Latin America target an optimized sodium and potassium intake. The aims of this study were to assess the sodium and potassium intake using 24-hour urinary analysis and to study their association with blood pressure in a Uruguayan population cohort using cluster analysis. A total of 149 participants (aged 20-85 years) were included in the study, and office blood pressure, anthropometric measurements, biochemical parameters in the blood, and 24-hour urine samples were obtained. The overall mean sodium and potassium excretion was 152.9 ± 57.3 mmol/day (8.9 ± 3.4 g/day of salt) and 55.4 ± 19.6 mmol/day, respectively. The average office systolic/diastolic blood pressure was 124.6 ± 16.7/79.3 ± 9.9 mmHg. Three compact spherical clusters were defined in untreated participants based on predetermined attributes, including blood pressure, age, and sodium and potassium excretion. The major characteristics of the three clusters were (1) high systolic blood pressure and moderate sodium excretion, (2) moderate systolic blood pressure and very high sodium excretion, and (3) low systolic blood pressure and low sodium excretion. Participants in cluster three had systolic blood pressure values that were 23.9 mmHg (95% confidence interval: -29.5 to -1.84) lower than those in cluster one. Participants in cluster two had blood pressure levels similar to those in cluster one (<i>P</i> = 0.32) and worse metabolic profiles than those in cluster one and three (<i>P</i> < 0.05). None of the clusters showed high blood pressure levels and high sodium excretion. No linear association was found between blood pressure and urinary sodium excretion (r < 0.14; <i>P</i> > 0.47). An effect of sodium and potassium intake on blood pressure levels was not found at the population level using regression or cluster analysis.
Project description:Salt intake over reference level would result in elevated blood pressure (BP) and long-term morbidity. Salt meter is a device used to detect sodium content in daily food. This study aimed to evaluate the efficacy of salt-meter addition to dietary education. The authors conducted a randomized-controlled trial in hypertensive patients with uncontrolled BP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg). Patients were randomized to receive salt meter plus dietary education (group A) or education only (group B), and followed up for 8 weeks. The primary endpoint was change in 24-h urinary sodium excretion. Changes in BP, salt taste sensitivity, cardio-ankle vascular index (CAVI) were also analyzed. There were total number of 90 patients who had complete follow-up, 45 in each group. Mean age was 62.9 years and 53% were females. Mean baseline 24-h urine sodium was 151.6 mmol/24 h and mean SBP and DBP were 152.8 and 83.4 mmHg, respectively. Baseline characteristics were similar between two groups. At 8 weeks, mean change in urine sodium were -31.83 mmol/24 h and 0.36 mmol/24 h in group A and group B, respectively (p = .006). Mean decrease in BP were SBP, 14.44 versus 8.22 mmHg (p = .030), and DBP 5.53 versus 1.93 mmHg (p = .032). The salt sensitivity was improved more in group A. There was no different between change in CAVI. From this study, salt meter in conjunction with dietary education, for self-monitoring of salt intake is superior to education alone in hypertensive patients, and provided better blood pressure control. Salt meter should be considered in uncontrolled hypertensive patients.
Project description:In this cross-sectional study, we hypothesized that hemodialysis patients consuming greater processed meat is associated with hypertension risk, which can be partly explained by the high sodium content in processed meat. From September 2013 to May 2014, one hundred and four patients requiring chronic hemodialysis treatment were recruited from hemodialysis centers. Data on systolic blood pressure and diastolic blood pressure before receiving dialysis, and 3-day dietary records of the recruited patients were collected. HD patients with systolic and diastolic blood pressures greater than140 mmHg and higher than 90 mmHg, respectively, were considered hypertension risk. Protein foods were divided into 4 categories: red meat, white meat, soybeans, and processed meat (e.g., sausage and ham). In a model adjusted for energy intake and hypertension history, additional servings of processed meats was positively associated to systolic blood pressure >140 mmHg (odds ratio [95% confidence interval]: 2.1 [1.0-4.3]), and diastolic blood pressure > 90 mmHg (odds ratio: 2.5 [1.2-5.5]). After adjustment for dietary sodium contents or body mass index (BMI), most associations were substantially attenuated and were no longer significant. In systolic blood pressure greater than140 mmHg, one serving per day of red meats (? = -1.22, P < .05) and white meats (? = -0. 75, P = .05) was associated with a reduced risk compared with one serving per day of processed meats. Similarly, compared with one serving per day of processed meat, a reduced risk of diastolic blood pressure higher than 90 mmHg was associated with one serving per day of red meat (? = -1. 59, P < .05), white meat (? = -0. 62, P < .05). Thus, in these hemodialysis patients, intake of processed meat is significantly positively associated with higher blood pressure risk, and both sodium contents in processed meat and BMI significantly contributes to this association.
Project description:<h4>Background and objectives</h4>Transfusion-associated circulatory overload (TACO) is the primary cause of transfusion-related mortality. Speed and volume of transfusion are major risk factors. The aim of this study was to investigate the interaction of red blood cell (RBC) transfusion speed and volume on the development of TACO.<h4>Materials and methods</h4>A validated model for TACO in anaemic Lewis rats with an acute myocardial infarction was used. The effect on pulmonary hydrostatic pressure of one, two or four units of packed RBCs transfused in either 30 or 60 min was evaluated (3.3-26.6 ml·kg<sup>-1</sup> ·hr<sup>-1</sup> ). Pulmonary capillary pressure was measured as left ventricular end-diastolic pressure (LVEDP). Cardiac stress biomarkers atrial natriuretic-peptide (ANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured 1-h post-transfusion.<h4>Results</h4>Thirty animals were included (n = 5 per group). Transfusion of RBCs increased LVEDP in a volume-dependent manner (ΔLVEDP [mmHg]: -0.95, +0.50, +6.26, p < 0.001). Fast transfusion increased overall ΔLVEDP by +3.5 mmHg and up to +11.8 mmHg in the four units' group (p = 0.016). Doubling transfusion speed increased ΔLVEDP more than doubling volume in the larger volume groups. No difference in ANP or NT-proBNP were seen in high transfusion volume or groups.<h4>Conclusion</h4>Transfusion volume dose-dependently increased LVEDP, with speed of transfusion rapidly elevating LVEDP at higher transfusion volumes. ANP and NT-proBNP were not impacted by transfusion volume or speed in this model. TACO is seen as purely volume overload, however, this study emphasizes that limiting transfusion speed, as a modifiable risk factor, might aid in preventing TACO.
Project description:The incidence of Hypertension as a major cardiovascular threat is increasing. The best known diet for hypertensives is 'no added salt diet'. In this study we evaluated the effect of 'no added salt diet' on a hypertensive population with high dietary sodium intake by measuring 24 hour urinary sodium excretion.In this single center randomized study 80 patients (60 cases and 20 controls) not on any drug therapy for hypertension with mild to moderate hypertension were enrolled. 24 hour holter monitoring of BP and 24 hour urinary sodium excretion were measured before and after 6 weeks of 'no added salt diet'.There was no statistically significant difference between age, weight, sex, Hyperlipidemia, family history of hypertension, mean systolic and diastolic BP during the day and at night and mean urinary sodium excretion in 24 hour urine of case and control groups. Seventy eight percent of all patients had moderate to high salt intake. After 6 week of 'no added salt diet' systolic and diastolic BP significantly decreased during the day (mean decrease: 12.1/6.8 mmhg) and at night (mean decrease: 11.1/5.9 mmhg) which is statistically significant in comparison to control group (P 0.001 and 0.01). Urinary sodium excretion of 24 hour urine decreased by 37.1 meq/d +/- 39,67 mg/dl in case group which is statistically significant in comparison to control group (p: 0.001). Only 36% of the patients, after no added salt diet, reached the pretreatment goal of 24 hour urinary sodium excretion of below 100 meq/dl (P:0.001).Despite modest effect on dietary sodium restriction, no added salt diet significantly decreased systolic and diastolic BP and so it should be advised to every hypertensive patient.Clinicaltrial.govnumber NCT00491881.
Project description:Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In salt-sensitive HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155-138 mm?Hg; P=0.02) and diastolic blood pressure (79-72 mm?Hg; P=0.04), 24-hour ambulatory systolic (130-123 mm?Hg; P=0.02) and diastolic blood pressure (67-62 mm?Hg; P=0.02), and carotid-femoral pulse wave velocity (12.4-11.0 m/s; P=0.03). Urinary F2-isoprostanes decreased by 31% (209-144 pmol/mmol Cr; P=0.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of salt-sensitive hypertension, a phenotype present in many HFPEF animal models and suggest shared pathophysiological mechanisms linking these 2 conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.