ORIGINAL ARTICLE Increased blood pressure reactivity to dietary salt in patients with the metabolic syndrome IS Hoffmann 1 and LX Cubeddu 1,2 1 Center for the Detection and Treatment of Silent Risk Factors for Cardiovascular and Metabolic Diseases, School of Pharmacy, Central University of Venezuela, Caracas, Venezuela and 2 Department of Pharmaceutical Sciences, College of Pharmacy, Health Professions Division, NOVA Southeastern University (NSU), Fort Lauderdale, FL, USA The metabolic syndrome is a predictor of type II diabetes mellitus and cardiovascular disease. The mechanisms of the increased blood pressure (BP) in patients with the metabolic syndrome are poorly understood. We investi- gated if salt-sensitivity is a characteristic of the metabolic syndrome. A total of 301 subjects (87male subjects, 214 female subjects) of 41.570.7 years of age completed a salt sensitivity test, and were evaluated for the presence of metabolic syndrome. BP and 24-h sodium excretion were obtained under usual, high- and low-salt intakes. BP reactivity to salt was markedly increased in subjects with the metabolic syndrome; its magnitude was directly related to the severity of the syndrome. Reducing dietary salt from the average usual intake (8.2g/day) to nearly 2.3 g/day lowered systolic blood pressure (SBP) by 8.771.3mm Hg in subjects with four and five traits, 6.071.1 in those with three traits and failed to modify the BP of subjects with one or no traits of the syndrome (Po0.0001). Salt restriction reduced the percentage of subjects with metabolic syndrome that were hypertensive (8.2g/day of salt) from 23.8 to 8.2% (v 2 : 23.6; Po0.0001). BP of non-hypertensive subjects with metabolic syn- drome was also significantly reduced by salt restriction (7.171.5 and 4.271.1mm Hg in those with four or five traits and three traits, respectively). In conclusion, the metabolic syndrome is a strong clinical predictor of salt sensitivity. The enhanced BP reactivity to dietary salt observed in subjects with the metabolic syndrome, may determine the increased BP levels commonly associated with the syndrome. Journal of Human Hypertension (2007) 21, 438–444. doi:10.1038/sj.jhh.1002153; published online 1 February 2007 Keywords: metabolic syndrome; salt sensitivity; blood pressure; salt intake Introduction The metabolic syndrome is a highly prevalent condition characterized by a cluster of risk factors, and is associated with the development of type II diabetes and cardiovascular disease. 1–5 Central obesity, reduced high-density lipoprotein (HDL) cholesterol, increased triglycerides, high blood pressure (BP) and abnormal glucose metabolism 6 are among the traits used in defining the syndrome. The mechanisms underlying the increase in BP associated with the metabolic syndrome are poorly understood, and are addressed in this study. The BP reactivity to salt, also known as salt sensitivity varies considerably between indivi- duals. 7–9 Exaggerated BP reactivity to salt, known as salt sensitivity, is associated with increased risk for cardiovascular events. 10–14 Although genetic and acquired factors play a role in the pathogenesis of salt sensitivity, its aetiology is unknown. Older age and insulin resistance have been reported to be associated with salt sensitivity. 7,8,15–19 As insulin resistance is the landmark of the metabolic syn- drome, 20,21 we proposed that salt sensitivity is more prevalent in subjects with than in subjects without the syndrome. To test our hypothesis, salt sensitivity testing was used to compare the BP reactivity to salt of subjects with and without the metabolic syn- drome. If our hypothesis is correct, salt restriction could be an integral part of the treatment for patients with the metabolic syndrome. Materials and methods Study population Voluntary subjects of 18–70 years of age, living in the city of Caracas, and attending the Center for the Detection and Treatment of Silent Risk Factors for Cardiovascular and Metabolic Diseases, from 1999 Received 14 November 2006; revised 16 December 2006; accepted 18 December 2006; published online 1 February 2007 Correspondence: Dr LX Cubeddu, HPD, Department of Pharma- ceutical Sciences, Nova Southeastern University; 3200 S Uni- versity Dr, Ft. Lauderdale, FL 33328, USA. E-mail: lcubeddu@nova.edu Journal of Human Hypertension (2007) 21, 438–444 & 2007 Nature Publishing Group All rights reserved 0950-9240/07 $30.00 www.nature.com/jhh