Tiny Jaarsma Linköping University No conflict of interest

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1 Detrimental effects of sodium in heart failure - Tiny Jaarsma Linköping University No conflict of interest

3 Sodium restriction in Heart Failure Why? Prevention of heart failure Blood pressure treatment trials of 2 5 years have demonstrated that lowering BP could reduce heart failure by over 50%. He, et al., EHJ 2011; Chobanian et al., Hypertension 2003

4 Sodium and heart failure He F J et al. Eur Heart J 2011;32:

5 Sodium restriction in Heart Failure Why? Prevention of heart failure Blood pressure treatment trials of 2 5 years have demonstrated that lowering BP could reduce heart failure by over 50%. Prevention of deterioration and complications Improve outcomes He, et al., EHJ 2011; Chobanian et al., Hypertension 2003

6 Sodium restriction: beneficial or harmful? beneficial harmful

7 Arterial underfilling with resultant neurohumoral activation and renal sodium and water retention. Bansal S et al. Circ Heart Fail 2009;2: Copyright American Heart Association

8 Effects of sodium intake in heart failure: low-sodium intake may have varied effect on heart failure. Gupta D et al. Circulation 2012;126: Copyright American Heart Association

9 Sodium restriction? beneficial

10 Sodium restriction beneficial? Arcand et al., Journal of Clinical Nutrition 2011

11 Sodium restriction beneficial? 123 medically stable patients with systolic HF Multiple day food records at 2 time points Endpoints: HF hospitalization / HF ER visit, all-cause hospitalization and death or transplantation. 3 year follow-up Sodium: <1.9 g Na/d (n = 41) Na/d (n = 41) >2.8 Na/d (n = 41) Arcand et al., Journal of Clinical Nutrition 2011

12 Arcand et al., Journal of Clinical Nutrition 2011

13 Sodium restriction beneficial? Heart failure patients who consumed a high sodium diet (2.8 g Na/d), compared with patients who consumed lower amounts of dietary sodium, had a higher incidence of early advanced HF. Patients who consumed a high-sodium diet had a 2.5-fold increased risk of advanced HF and an elevated risk of all-cause hospitalization and mortality when adjusted for covariates Arcand et al., Journal of Clinical Nutrition 2011

14 Sodium restriction beneficial? 302 HF patients 24-hour urine sodium to indicate sodium intake Endpoints: Event-free survival 1 year follow-up Sodium: >3g UNa and < 3 f UNa Lennie et al., Journal of Cardiac Failure 2011

15 24-hour Urinary Sodium Excretion Lennie et al., Journal of Cardiac Failure

16 Lennie et al., Journal of Cardiac Failure 2011

17 Lennie et al., Journal of Cardiac Failure 2011

18 Sodium restriction? harmful

19 Sodium restriction harmful?

20 Sodium restriction harmful? 232 compensated HF patients Furosemide mg ml fluid restriction 180 days of follow-up. Randomized into two groups: group 1 (n= 118) normal sodium diet (120 mmol of sodium = 2.8 g) group 2 (n= 114) low-sodium diet (80 mmol of sodium =1.8 g) Endpoints: worsening HF (primary end point). Readmissions and mortality, plasma BNP, aldosterone levels, and PRA (plasma renin activity) Paterna et al., 2008

21 Sodium restriction harmful? At 180 days,: Low (1.8 g) sodium diet group had higher B-type natriuretic peptide levels higher aldosterone levels experienced a 44% increase in plasma rennin activity from baseline At 12-month Low (1.8 g) sodium diet group had similar neurohormonal activation higher rates of hospital admissions or death higher levels of the proinflammatory cytokines Paterna et al., 2008, Parrinello 2009

22 normal-sodium diet improves outcome, and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated HF patients. Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet. NB strong fluid restriction, low betablockers Paterna et al., 2008

23 Paterna et al., 2009

24 Paterna et al., 2009

25 Paterna et al., 2009

26 Group A showed the best results, with a significant reduction (p <0.001) in readmissions, BNP, aldosterone, and plasma renin activity compared with the other groups during follow-up (p <0.001). Paterna et al., 2009

27 Paterna et al., 2009

28 Salt-fluids-diuretics?

29 Sodium restriction: beneficial or harmful?

31 Physiological and Neurohormonal Responses Inconsistent with regard to cardiac index Natriuretic peptide levels were affected inconsistently among studies; Levels of neurohormones increased with dietary sodium restriction regardless of degree of restriction Diuresis, Electrolyte, and Renal Responses low dietary sodium intake -> increase in blood urea nitrogen and creatinine, whereas moderate-to-high sodium intake was related to decreased creatinine HF or non-hf readmission rates and mortality rates Inconsistent in several studies. Mortality rate was lower in the moderate-to-high sodium group in 3 studies in comparison with lowsodium diet. Gupta et al.,

32 HF patients want more salt? Angiotensin II (ANG II) the major effector peptide of the RAAS acts on and in the brain to stimulate both thirst and salt appetite Does circulating ANG II and/or aldosterone act to enhance the motivation to consume excess salt under conditions such as HF? HF patients may actually have an enhanced avidity or preference for salty tastes that may drive excess salt consumption and low compliance with low sodium diets.. De Souza, 2012

33 Taste? Method Case-control prospective study including 38 patients with clinically stable HF NYHA II or III 25 healthy volunteers Bean soup with varying salt content De Souza, 2012

34 1. Questionnaire on food preferences 2. Preference test: salt concentrations (0.58, 0.82, and 1.16 g/100 g) of bean soup were presented to the subjects De Souza, 2012

35 HF patients want more salt? HF outpatients as compared to healthy volunteers had an increased preference for salt as indicated by their preferred concentration of salt contained in a bean soup preparation. HF patients also actually disliked soup with a low concentration of salt. It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt. De Souza, 2012

36 37

37 Conclusion We do know that very high sodium intake is not optimal, but we do not know (1) what the lower safest and most efficacious range is and (2) if that range would be applicable to all patients, or needs to be individualized Gupta et al., 2012

38 What do the new guidelines say? (2012) McMurray et al. EJHF & EHJ

39 40

Akash Ghai MD, FACC February 27, No Disclosures

Akash Ghai MD, FACC February 27, 2015 No Disclosures Epidemiology Lifetime risk is > 20% for American s older than 40 years old. > 650,000 new cases diagnosed each year. Incidence increases with age: 2%