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EPIDEMIOLOGY OF SALT AND HYPERTENSION

EPIDEMIOLOGY OF SALT AND HYPERTENSION. Arun Chockalingam Professor & Director of Global Health Secretary General, World Hypertension League. HTA 2008, 4 th International Symposium of Hypertension Santa Clara, Cuba May 27, 2008. Historical Information.

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EPIDEMIOLOGY OF SALT AND HYPERTENSION

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  1. EPIDEMIOLOGY OF SALT AND HYPERTENSION Arun Chockalingam Professor & Director of Global Health Secretary General, World Hypertension League HTA 2008, 4th International Symposium of Hypertension Santa Clara, Cuba May 27, 2008

  2. Historical Information • As long ago as 2,000 B.C., when the famous Chinese “Yellow Emperor” Huang Ti recorded salt’s association with a “hardened pulse”, we have known of a relationship between salt and blood pressure.

  3. Hemodynamics of Early Essential Hypertension

  4. Hemodynamics of Established Essential Hypertension

  5. Overall Scheme for Pathogenesis of Essential Hypertension

  6. Cardiovascular Events and Sodium Sensitivity Kaplan-Meier plots showing the relationship between total CV events in hypertensive patients and sodium sensitivity. p < 0.05 Morimoto et al, Lancet 1997; 350: 1734

  7. Urinary Salt Excretion and Death From strokes in 12 European countries Adapted from Perry, IJ et al. J Hum Hypertens, 1992; 6:23-25

  8. Hazard Ratios association of a 6 g/day increase in salt intake with 24-h urinary Na+ excretion Increased risk of death related to a 6 g/day increase in salt intake (N=2436) CHD Death CVD Death All Death 1.75 1.50 High salt intake 1.25 Hazard Ratio ¶ 1.00 Lower salt intake 1.75 0.50 *** P<0.001 compared to lower salt intake ¶ Adjusted for age, study year, smoking, serum total and HDL cholesterol, systolic blood pressure, and body mass index He FJ, MacGregor GA. a meta-analysis of randomized trials. Implications for public health. J Hum Hyptens 2002;16:761-770

  9. Relationship between the net change in urinary Na+ and SBP • 4 2 0 -2 Change in Systolic Blood Pressure (mmHg) -4 Normotensives -6 -8 Hypertensives -10 -12 -30 -50 -70 -90 -110 -130 Change in Urinary Sodium (mmol/24h) The yellow circles represent normotensives and the blue circles represent hypertensives. The slope is weighted by the inverse of the variance of the net change in systolic blood pressure. The size of the circle is in proportion to the weight of the trial. He FJ, MacGregor GA. a meta-analysis of randomized trials. Implications for public health. J Hum Hyptens 2002;16:761-770

  10. Dose-response relation between 24-h urinary Na+ and BP in two studies Double-blind salt reduction study & the DASH-Sodium study He, FJ et al. Hypertension 2003; 42:1093-109 DASH: Dietary Approaches to Stop Hypertension 79 Vs 81 HT/116 Vs 121 HT Double-blind study: 3 salt intakes, each 4 wks 19 HT

  11. Comparison of the dose-response relation among 3 studies • Double-blind salt reduction study • DASH-Sodium study • Metal-analysis of modest salt reduction > 4 wks He, FJ et al. Hypertension 2003; 42:1093-109

  12. Weekly group ave. SBP at lower Na+ level compared with group ave. SBP measured at end of higher Na+ level (SBP mean 95% CI), (n=188); 60% NT Age> 45: 65%; 55% F; 58% Black Obarzanek, E et al. Hypertension 2003; 42:459-467

  13. Mean SBP changes in the DASH-Na+ trial Solid lines indicate the effects of sodium reduction in the 2 diets; hatched lines, the effects of the DASH diet at each sodium level Adapted from Sacks, FM et al. N Engl J Med 2001; 344:3-10

  14. BP by week during the DASH feeding study in 3 diets Adapted from Appel, LJ et al. N Engl J Med 1997; 336:1117-1124

  15. % change in MAP in normotensive subjects receiving incremental increases in Na+ Blood pressure at the end of 7 days of low (10 mmol/d) salt intake was taken as baseline. All subjects demonstrated an increase in blood pressure with salt loading. Data adapted from Luft et al. Circulation 1979; 60:697-706

  16. Key Messages From Intersalt Study • Strong positive associations of 24 hr urinary Na excretion to BP of individuals, to median BP across its 52 population samples, and to differences in BP with age. • The within population association of Na to BP in Intersalt are concordant with the cross population findings for 52 samples. • Estimates of the effect of median Na excretion higher by 100 mmol/day over a 30 year period (age 55 minus age 25) were a greater difference of 10-11 mm Hg in SBP and 6 mm Hg in DBP. • These results lend further support to recommendations for mass reduction of high salt intake for the prevention and control of adverse blood pressure levels and high blood pressure in populations. Elliott, P et al. BMJ 1996; 312:1249-1253

  17. TONE Study Baseline BP and Change From Baseline to Last Visit Prior to Attempted Medication Withdrawal TONE: Trial of Nonpharmacologic Interventions in the Elderly *Change in BP calculated For 953 participants who attended at least 1 study visit after Randomization. p<.001 bet UC & IG for SBP or DBP Age: 60-80 yrs; BP < 145/85 + 1 Rx Whelton, PK et al. JAMA 1998, 279(11):839-846

  18. CV Events During Follow-up of TONE Participants According to Intervention Assignment Trial of Nonpharmacologic Interventions in the Elderly Whelton, PK et al. JAMA 1998, 279(11):839-846

  19. TONE Study - Mean change in 24-h urinary Na+ excretion Na+ reduction group: n=487 No Na+ reduction group: n=488 Error bars indicate SEMs. The numbers used in the figure are given in mmol/d Trial of Nonpharmacologic Interventions in the Elderly Whelton, PK et al. JAMA 1998, 279(11):839-846

  20. Trial of Nonpharmacologic Interventions in the Elderly (TONE): Mean change in Body weight Weight loss group: n= 291 No weight loss group: n= 291 Whelton, PK et al. JAMA 1998, 279(11):839-846 Error bars indicate SEMs. The numbers used in the figure are given in kg

  21. TONE: % of people free of CV events and HBP and did not have antihyp. therapy during follow-up Whelton, PK et al. JAMA 1998, 279(11):839-846

  22. Change in SBP & DBP (mm Hg) achieved in trials of 13 to 60 months Systematic review of LT effects of advice to reduce dietary salt in adults: Meta analysis of RCTs Hooper at al. BMJ 2002; 325:628-636

  23. Change in urinary Na+ (mmol Na/24 hours) achieved in trials of 6 to 12 months, 13 to 60 months, and >60 months Hooper at al. BMJ 2002; 325:628-636

  24. Systematic review of LT effects of advice to reduce dietary salt in adults: Meta analysis of RCTs • Intensive interventions, unsuited to 1o care or pop. prevention pgms, provide ONLY a small reduction in BP and Na+ excretion. • Effects on deaths and CV events are unclear. • Advice to reduce Na+ intake may HELP people on antihypertensive drugs to stop their meds. while maintaining good BP control. Hooper at al. BMJ 2002; 325:628-636

  25. M-mode echocardiographic LV mass Pop-based study focused on lifestyle & salt intake Random sample (51F+ 42M) 7-day food record Conclusion: Synergistic interaction of dietary salt with BP suggests high Na+ intake may sensitize the heart to the hypertrophic stimulus of pressure load Correlation between salt intake and LV mass in subjects with SBP >121 mm Hg Adapted from Kupari P et al J. Circulation, 1994; 89:1041 – 1050

  26. Background:High salt and nitrate intake are RFs for CaS. Little is known of their possible interaction. Methods: Randomly selected 24-hr urine from 39 pop (5756 for Na+ and 3303 for nitrate) from INTERSALT study. Regression analyses in relation to national CaS mortality rates. Conclusion: Salt intake is likely the rate-limiting factor for CaS mortality at population level. The relation of urinary salt excretion to cancer of the stomach (CaS) Adapted from Joossens, JV et al. Int J Epidemiol, 1996; 25 494-504

  27. Salt and Essential Hypertension • Essential hypertension is seen primarily in societies with average salt intakes of more than 50meq/day (2.3 g sodium). • Essential hypertension is rare in societies with average salt intakes of less than 50meq/day (1.2 g sodium). • These observations suggest that the development of hypertension requires a threshold level of salt intake. Elliott P, Stamler J, Nichols R et al. Intersalt revisited: Further analyses of 24 hour sodium excretion and blood pressure within and across populations. BMJ 1996; 312:1249

  28. Decrease in salt intake (g) calculated from urinary Na+ excretion among Finns Linear Regression Analyses (adjusted by age & Survey area): Annual decrease among men: 0.14 g (p<0.001); Women: 0.11 g (p<0.0001) Only N.Karelia, Kuopio & SW Finland are included in the analysis Laatikainen, T et al. European Journal of Clinical Nutrition 2006; 60:965-970

  29. National Policy Intervention “The experience of Finland, which has had a salt reduction program running since the late 1970s, shows that population-wide reduction of dietary salt leads to population-wide reductions in blood pressure and parallel reductions in deaths from stroke and heart disease.” --- Professor Graham MacGregor, Chairman of WASH

  30. Demographic Factors Influencing Salt Sensitivity • Race: Blacks have been consistently shown to have a greater frequency of salt sensitivity than Whites. • Age: Increasing salt sensitivity has been noted with increasing age. This relationship appears to be stronger in hypertensive than in normotensive individuals. Weinberger, M.H. Hypertension 1996, 27:481-490

  31. Familial and Genetic Factors • Salt sensitivity was more likely to be observed in individuals with the homozygous haptoglobin 1-1 genotype than in those with the 2-2 genotype and that individuals with the heterozygotic 2-1 genotype had responses that were intermediate between the other two groups. Weinberger, M.H. Hypertension 1996, 27:481-490

  32. Physiological Factors Associated with Salt Sensitivity • Renal Function • The Renin-Angiotensin-Aldosterone System • Atrial Natriuretic Factor • The Sympathetic Nervous System • Adrenergic Receptors • Endothelin and Nitric Oxide • Ion Transport • Insulin Weinberger, M.H. Hypertension 1996, 27:481-490

  33. Deaths averted by population-level intervention Asaria et al. Lancet 2007; 370: 2044-53

  34. Salt & tobacco reduction: Estimated Deaths averted/100K pop (2006-15) Population older than 30 yrs of age Asaria et al. Lancet 2007; 370: 2044-53

  35. Cost to implement the package of intervention Asaria et al. Lancet 2007; 370: 2044-53

  36. Key messages • 23 countries have 80% of burden of CNCD in LMI regions of the world. • In these countries 13.8 m deaths could be averted over 10 yrs (8.5 m by salt reduction and 5.5 by implementing FCTC) • Most deaths averted would be from CVD 975.6%) followed by Resp dis (15.4%) and cancer (8.7%). • Cost to implement both strategies would be $ 0.4 in LMIC and $ 0.5-1.0 in UMIC (as of 2005). Asaria et al. Lancet 2007; 370: 2044-53

  37. SUMMARY • Across populations, the level of blood pressure, the incremental rise in blood pressure with age, and the prevalence of hypertension are related to sodium intake. • Observational studies and RCTs document a consistent effect of sodium consumption on blood pressure. Modest reduction in average sodium intake (from 31 to 44 mmol/d) decreases the percentage of prehypertension. • Blood pressure is also affected by many other variables, and a reduced sodium intake is only ONE component of recommended strategies to lower blood pressure. Report of the AMA Council on Science and Public Health Dickinson, B et al. Arch Intern Med 2007; 167(14):1460-1468

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