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Salt and Hypertension M.R.ABBASI MD,Nephrologist NRC TUMS 1993 Natrium=Sodium(Na) a metalic element with mol.Wt. 23gr Chloride(Cl) a light green toxic gas with mol. Wt. of 35.5gr TUMS-Nephrology Research Center 5 TUMS-Nephrology Research Center 6 Forms of Sodium • • 90% of sodium consumed as sodium chloride (salt, common salt, table salt,Halite) Other forms: – sodium bicarbonate – sodium in processed foods, such as sodium glutamate, sodium benzoate, sodium phosphate Sodium Balance The human body contains 1 gr Na / Kg of BW • 70 gr Νa = ~ 3000 mmol = 3000 meq Na • Sodium is located to 95% extracellularly and to 5% intracellularly. Every 6 gr salt contains 2.3 gr( 100mmol=100meq ) of Na • NaCl • • • • • Salt is composed of 40% Na and 60% Cl. Sodium together with potassium is an essential mineral for regulating body fluid balance. It is also essential for the transmission of the nerve and muscle impulses. Physiologic need of salt is only about 0.5 gr/day(current use is 9-12gr). High salt using is an acquired addiction for salt by consumption of processed foods. • Adverse Effects of Excess Salt Intake Established relationship – Increased blood pressure → CVD and Stroke • Probable relationship – Gastric and Colorectal cancer • Suggestive relationship – Increased risk of osteoporosis – Increased risk of nephrolithiasis – Increased left ventricular mass • Hypothesized relationship – Overweight/obesity – asthma P. A. Gilbert* and G. Heiser: Salt and health British Nutrition Fundation The association between a high salt intake and hardened pulse was already known 4500 years ago . Cirillo M, Capasso G, Di Leo VA, De Santo NG Research . A history ofTUMS-Nephrology salt. Am J Nephrol 1994;14:426Center 431. 14 Magnitude of BP Problem: Population Perspective • • • Worldwide, cardiovascular disease (heart disease and stroke) is the leading cause of death 62% of strokes and 49% of CAD events attributed to elevated BP* 26% of adults worldwide (972 million) have hypertension** *WHO, World Health Report 2002: Reducing Risks, Promoting Healthy Life, **Kearney Lancet 2005;305:217 Leading Causes of Death, Worldwide in 2002 Cardiovascular diseases Infectious and parasitic diseases Cancer Respiratory infections Respiratory diseases Unintentional injuries Perinatal conditions Digestive diseases Intentional injuries Neuropsychiatric conditions Diabetes mellitus Genitourinary diseases Maternal conditions Congenital anomalies Nutritional deficiencies Others 0 2000 4000 Research 6000 8000 10000 12000 14000 TUMS-Nephrology Center Number of deaths (x1000) 16000 18000 16 Major Underlying Factors causing Death - Worldwide Raised Blood Pressure 7 million Tobacco High cholesterol Underweight Unsafe sex Low fruit & vegetables intake High BMI Developed region Physical inactivity Developing region Alcohol Unsafe water, sani & hygiene 0 1 2 3 4 5 TUMS-Nephrology Research Millions of Deaths Ezzati et al. Lancet 2002:360:1347-60. Center 6 7 17 Types of Evidence Relating Salt Intake to Blood Pressure Epidemiology Over 50 population studies Migration Several Genetic All defects identified so far impair the ability of the kidney to excrete salt. Animal All forms of hypertension are caused or aggravated by salt [rats, chimpanzees] Trials Children: ~10 trials, one trial in infants Adults: > 50 trials Population Interventions several TUMS-Nephrology Research Center 18 • Primary hypertension is seen primarily in societies with average sodium intakes above 100 meq/day (2.3 g sodium( • HTN is rare in societies with average sodium intakes of less than 50 meq/day (1.2 g sodium) • • HTN requires a threshold level of sodium intake. • This effect appears to be independent of other risk factors for hypertension, such as obesity. SBP Slope with Age (mmHg/yr) by Median Na Excretion in 52 Communities Worldwide Systolic blood pressure slope with age (mm Hg/year) 1.4 1.2 1.0 Populations with No Rise in SBP with Age 0.8 0.6 0.4 0.2 0.0 -0.2 -0.4 0 1,150 2,300 3,450 Research MedianTUMS-Nephrology sodium excretion (mg/24h) INTERSALT BMJ 1988;297:319 Center 4,600 5,750 20 Predicted Benefits of Reducing Sodium on Stroke and Heart Attack Deaths • Reducing sodium by 400 mg/day would reduce strokes by 5% heart attacks by 3% • Reducing sodium by 2,400 mg/day would reduce strokes by 24% heart attacks by 18% Hypertension TUMS-Nephrology Research Center 2003;42:1093-99 21 Effects of Reduced Na on CVD Events: Results from 3 Randomized Trials INTERVENTION OUTCOME TONE1 (2001) 639 Elderly Veterans2 Taiwan (2006) 1,981 Elderly TOHP Follow-up3 (2007) 3,126 Prehypertensives ↓ Na ↓ Na /↑ K Salt ↓ Na 21% ↓ CVD events 2.3 yrs 41%* ↓ CVD Mortality 2.6 yrs 30%* ↓ 10-15 yrs CVD events *p<0.05 1Appel, FU Arch Int Med, 2001; 2Chang, AJCN, 2006; 3Cook, BMJ, 2007 Meta-Analyses of the Effect of Salt Reduction on Blood Pressure. Kotchen TA et al. N Engl J Med 2013;368:1229-1237. Projected Estimates of Comparative Effect of Various Population Interventions on Annual Reductions in Cardiovascular Events. Bibbins-Domingo K et al. N Engl J Med 2010;362:590-599. Estimated Changes in Systolic Blood Pressure Associated with Reductions in Dietary Salt. Bibbins-Domingo K et al. N Engl J Med 2010;362:590-599. Estimated Changes in Systolic Blood Pressure Associated with Reductions in Dietary Salt. Bibbins-Domingo K et al. N Engl J Med 2010;362:590-599. Effects of Sodium Reduction in Children: Results of a Meta-Analysis • 10 Trials • 966 Children • Mean age=14 • Median duration = 20wk • 42% Reduction in Na He and MacGregor, HTN 2006 Salt sensitivity BP responsiveness to variations in salt intake is known as salt sensitivity. 30-50% of hypertensives and a smaller percentage of normotensives are thought to have salt sensitive BP. • Factors Associated with Increased Salt Sensitivity • Fixed factors – – – – African-Americans Middle and older-aged persons Genetic Factors Individuals with: • • • • • Hypertension Diabetes Chronic Kidney Disease Low birth Wt Modifiable – – – – Low potassium intake Low Calcium intake Poor quality diet Obesity and metabolic syndrom. Na sensitivity associated with: • • • • Insulin resistance Dyslipidemia Microalbuminuria Subtle renal injury The fundamental defect in all hypertension is the kidneys' inability to excrete the excessive sodium load imposed by a high-salt diet. (He & MacGregor, 2007). Interrelated Salt-Induced Alterations That May Impair Sodium Excretion and Promote Vasoconstriction. Kotchen TA et al. N Engl J Med 2013;368:12291237. Sodium retention(mechanisms) • • • • Increase activity of the proximal NaH exchanger Increase Na reabsorption in thick ascending limb of henle loop by NaK-2Cl cotransporter Increase Na reabsorption by distal Na-Cl cotransporter Increase Na reabsorption by ENaC in the collecting tubule. Effect of low potassium diet • • • Low K intake may increase the effect of Na on BP . Urinary Na:K ratio is more important than urinary sodium excretion only. K excretion less than 50 mmol/day was associated with rising 3.4 mmHg in SBP and 1.9 mmHg in DBP.(INTERSALT study). Sodium and Potassium in the Pathogenesis of Hypertension Horacio J. Adrogué, M.D., and Nicolaos E. Madias, M.D.NEJM356;19. May10 2007 Hakuo Takahashi et al, The cntral mechanism underlyinh HTN: a revew of the role of Na ions, ENaC, the R-A-A system, oxidative stress and endogenous digitalis in the brain:HTN research (1160-34,1147)2011 Sodium and Potassium in the Pathogenesis of Hypertension Horacio J. Adrogué, M.D., and Nicolaos E. Madias, M.D.NEJM356;19. May10 2007 Sodium and Potassium in the Pathogenesis of Hypertension Horacio J. Adrogué, M.D., and Nicolaos E. Madias, M.D.NEJM356;19. May10 2007 Vasodilation failure • • Na loading causes vasodilation in Na insensitive subjects(by NO release). In Na sensitives Na loading causes an increase in Asymmetrical dimethylarginine which is endogenous inhibitor of NO. Sources of Dietary Sodium (62 adults who completed 7 day dietary records) Inherent 12% Food Processing 77% At the Table 6% During Cooking 5% Mattes and Donnelly, JACN, 1991; 10: 383 Na/K cotent of food Copyright 2005 Wadsworth Group, a division of Thomson Learning Food labelling Standard format : --group 1(Big4): energy, protein, carbohydrates and fat. --group2(4+4): sugars, saturated fat, fiber and sodium(and not salt). • There is a significant variation in the levels of salt consumption between countries, and also significantly different patterns of consumption. In European and North American countries the main sources of dietary salt are processed foods, restaurant services, and catering, while in Asian and African countries the main sources are the salt used in cooking and sauces. The food industry uses salt in every food category to enhance flavor, condition dough, preserve foods, and retain • World Action on Salt and Health(WASH) -increasing public awareness of the harmful effects of salt on health. -Reduction of salt use to less than 5-6 gr -getting food industry to decrease the amount of salt added to foods and clearing labelling on food products. Recommendations for Sodium Intake (mg/d): US and WHO US 2005 Dietary Guidelines General Population Hypertensives, blacks, adults (45+) World Health Organization < 2,300 (6gr salt) <1,500 (4GR salt) <2,000 (5gr Institute of medicine recommends: Na intake 65mmol(3.8gr NaCl) for<50yrs old, 55mmol(3.2gr salt) for 5170yrs old, 50mmol(2.9gr)/day for>70 yrs old + 120 mmol K(4.7gr) /day . Sodium and Potassium in the Pathogenesis of Hypertension Horacio J. Adrogué, M.D., and Nicolaos E. Madias, M.D.NEJM356;19. May10 2007 Thank You Nephrology Research Center