Genetic Epidemiology Network of Salt Sensitivity - GenSalt

Description:

Although some studies have suggested that a lower intake of dietary sodium reduces blood pressure, there is a substantial variation in individual response to a low-sodium diet. The GenSalt trial sought to study if there was an association between the metabolic syndrome and salt sensitivity of blood pressure.

Hypothesis:

The metabolic syndrome would be associated with a significantly higher risk of salt sensitivity.

Study Design

Study Design:

Patients Screened: 1,906
Patients Enrolled: 1,881
Mean Follow Up: 7 days
Mean Patient Age: 38.7 years
Female: 47

Patient Populations:

  • Patients ages 18-60 years
  • Mean systolic blood pressure between 130 and 160 mm Hg, mean diastolic blood pressure between 85 and 100 mm Hg, or both
  • No use of antihypertensive medications
  • Siblings, spouses, and offsprings were also recruited

Exclusions:

  • Stage 2 hypertension (≥160/100 mm Hg)
  • Secondary hypertension
  • Clinical cardiovascular disease
  • Diabetes
  • Chronic kidney disease
  • Pregnancy
  • Heavy alcohol consumption
  • Low-sodium diet
  • Use of antihypertensive drugs, antidiabetic drugs, or insulin

Primary Endpoints:

  • Mean blood pressure response

Secondary Endpoints:

  • Salt sensitivity (>5 mm Hg change in mean arterial blood pressure)

Drug/Procedures Used:

Study participants received a low-sodium diet (3 g sodium chloride [NaCl] per day) for 7 days, followed by a high-sodium diet (18 g NaCl per day) for an additional 7 days. Dietary potassium intake was unchanged.

Principal Findings:

A total of 1,881 participants volunteered for the study. Of these, 283 subjects met criteria for metabolic syndrome. Each subject received a low-sodium diet for 7 days (completed by 1,853 subjects), followed by a high-sodium diet for 7 days (completed by 1,845 patients). Patients with the metabolic syndrome were more likely to be older, female, with a sedentary lifestyle, with a higher body mass index, higher systolic and diastolic pressures, higher triglycerides and fasting glucose, and lower high-density lipoprotein cholesterol (p < 0.05 for all).

Age- and gender-associated blood pressure responses were significantly higher in the metabolic syndrome arm at days 2, 5, 6, and 7, and seemed to get larger with time. Moreover, as the number of metabolic risk factors increased, the age- and gender-associated responses to both systolic and diastolic blood pressure increased during both phases of the study. In the multivariate analysis, patients with four or five risk factors for the metabolic syndrome had a greater than threefold increased odds of high salt sensitivity (change in mean arterial pressure >5 mm Hg) during the low and high salt intervention periods (odds ratio [OR] 3.54, 95% confidence interval [CI] 2.05-6.11, p < 0.0001 following low-sodium intervention; OR 3.13, 95% CI 1.80-5.43, p = 0.0002 following high-sodium intervention).

Interpretation:

Although this is not a randomized controlled clinical trial, it is an interesting population-based dietary intervention study, which demonstrated a strong association between the metabolic syndrome and salt sensitivity of blood pressure in middle-aged subjects without diabetes. The incidence of salt-sensitive hypertension increased progressively with a higher number of risk factors for the metabolic syndrome. Multiple studies have demonstrated that patients with the metabolic syndrome have a higher risk of cardiovascular adverse outcomes, as well as of developing diabetes.

Furthermore, some studies have demonstrated a higher salt sensitivity as being associated with a higher risk of cardiovascular mortality. Hence, these results indicate that a low-sodium diet may be associated with a reduction in systolic and diastolic blood pressure in patients with one or more risk factors for the metabolic syndrome, and thereby, improved clinical outcomes. Underlying mechanisms for their findings, such as measurement of insulin resistance, were not explored, however.

References:

Chen J, Gu D, Huang J, et al., on behalf of the GenSalt Collaborative Research Group. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. Lancet 2009;Feb 13:[Epub ahead of print].

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Hypertriglyceridemia, Lipid Metabolism, Diet, Hypertension

Keywords: Multivariate Analysis, Arterial Pressure, Risk Factors, Blood Pressure, Insulin Resistance, Glucose, Sodium Chloride, Dietary, Metabolic Syndrome X, Diet, Sodium-Restricted, Body Mass Index, Sedentary Lifestyle, Potassium, Dietary, Triglycerides, Lipoproteins, HDL, Hypertension, Diabetes Mellitus, Fasting


< Back to Listings