Response to Letter to Editor
Response to “Salt: The Dying Echoes of the Food Industry” David A. McCarron,1 Alexandra G. Kazaks,2 Joel C. Geerling,3 Judith S. Stern,1,4 and Niels A. Graudal5
Correspondence: David A. McCarron ([email protected]). 1Department of Nutrition, University of California at Davis, Davis, California; 2Department of Nutrition and Exercise Science, Bastyr University, Kenmore, Washington; 3Department of Neurology, Beth Israel/ Deaconess Medical Center, Harvard University, Boston, Massachusetts; 4Department of Internal Medicine, University of California at Davis, Davis, California; 5Department of Rheumatology, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Initially submitted November 7, 2013; date of first revision November 12, 2013; accepted for publication November 13, 2013. doi:10.1093/ajh/hpt230 © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: [email protected]
primarily on the controversy regarding the effect of sodium intake reduction on cardiovascular disease (CVD) outcomes. Their basic premise is that “the issue is no longer whether reducing sodium (salt) is of public benefit, it is how best to reduce population salt intake.”1 That statement ignores the principle findings of the recent Institute of Medicine (IOM) report Sodium Intake in Populations,3 which challenged the scientific basis of the current US sodium guidelines. Cappuccio et al. suggest that our scientific data and findings, as well as those of the IOM, by inference, represent an ongoing conspiracy by the food industry that has included “biasing research findings, co-opting policy makers and health professionals, [and] lobbying politicians.” That grandiose hypothesis, by necessity in the case of our data, would mean the food industry manipulated the collections of several hundreds of thousands of 24-h UNaV samples from 69,011 individuals in 45 different countries for more than 5 decades. That allegation is, quite frankly, ludicrous. The opinion-based nature of Cap puccio et al.’s letter is evident in their challenges to the following issues, which they incorrectly characterize as “myths.” Issue 1. They offer no scientific data on the evolution of human sodium intake. Instead they cite the long-touted extrapolation of the very low sodium intake of an isolated primitive society with stunted growth, markedly elevated plasma renin activity (PRA) and aldosterone levels, short lifespan, and a history of extreme violence, including cannibalism.4 They provide no data for their contention that higher sodium intake is “recent” and ignore the clearly established findings in societies spanning several thousand years in which salt was a cornerstone of cultural and economic development.5
282 American Journal of Hypertension 27(2) February 2014
Issue 2. Cappuccio et al. provide no evidence challenging the cited physiological basis of our finding of a “normal range” for human sodium intake. The extensive evidence provided in our AJH paper— including findings from clinical trials6 and the neurosciences,7 the physiology of the relationship between PRA and 24-h UNaV,8 and documentation of the remarkable cultural diversity of 24-h UNaV clearly support the concept of a “normal range.” They offer no plausible, scientific explanation as to how nearly 70,000 people consuming the unique culinary characteristics of 45 countries observed for over 5 decades could possibly excrete sodium within such a narrow range unless it reflects tight physiologic control. Issue 3. The authors question our definition of the lower range of sodium intake. The 115 mmol/day we noted as representing the lower range of normal was defined by standard statistical analysis where 2 standard deviations defined the lower and upper range of the populations’ intake.2 Further, the “classic” PRA/UNaV data portrayed in Figure 3 of our article was derived directly from scientific data published in the New England Journal of Medicine in 1972.8 Published 40 years earlier, that data predicted, within 3 mmol/day, the mean human sodium intake the data in our article2 estimated. The study that Cappuccio et al. cite9 is most interesting not because it showed that modest sodium reduction in white hypertensive persons was associated with a significant increase in PRA, but for 2 other important points they mentioned in their article but not their letter. First, their recognition of the limited demographic variability in trials of sodium restriction is a critical issue. As noted in the IOM report, there is inadequate scientific data on the effects of
Downloaded from http://ajh.oxfordjournals.org/ at National Chung Hsing University Library on April 12, 2014
To the Editor: Cappuccio et al.’s letter, “Salt: The Dying Echoes of the Food Industry,”1 concerning our recent article2 does not address our article’s primary data or its analysis or provide any countervailing scientific data to argue against its interpretation. As our data indicated, “human sodium intake, as defined by 24-hour urinary sodium excretion (24-h UNaV), is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries.” In fact, several of the letter’s authors’ own reports provided scientific data included in our analysis.2 Furthermore, Cappuccio et al. offer no data to refute the decades of clinical and basic research we cited in support of the 24-h UNaV data characterizing a normal distribution of human sodium intake that is determined by appetite-control circuits in the brain, not the food supply. Instead, the authors extensively cite their many prior opinion pieces, none of which offers scientific data relevant to the concept of a “normal range of human sodium intake.” Their letter focuses
Response to Letter to Editor
determinations than food records or recalls used in National Health and Nutrition Examination Surveys (NHANES). The 24-h UNaV data from the other 44 countries describe the same stability even though the individual food supplies likely changed markedly over the timeframe of 5 decades. Issue 6. Cappuccio et al.’s claim of a reduction in the United Kingdom’s sodium intake belies the UK government’s numerous surveys that independent analyses established were simply variation around the mean.11,12 In either case, the change in the UK sodium intake the authors claim (1.5 g of salt or 25 mmol/day), readily falls within the normal range our article described. Cappuccio et al.’s additional claim that sodium reduction accounts for improvements in CVD outcomes is simply untrue, as indicated by the IOM report. The IOM panel based its findings on published data that measured 24-h UNaV and health outcomes over defined periods of time. The panel appropriately rejected, as simply theoretical estimates, the computer models frequently cited by advocates of sodium reduction.13,14 Cappuccio et al.’s claim that policies of sodium reduction in specific countries have been associated with dramatic reduction in CVD mortality is simplistic in its extrapolations. They ignore the reality that recent reports have demonstrated a 50% reduction in CVD death rates between 1980 and 2009 in 26 European countries,15 whereas our data indicate no change in 24-h UNaV in the majority of these same countries. Cappuccio et al. seem to have “cherry picked” examples that fit their argument. Extensive accusatory rhetoric directed at the food industry has been repeatedly voiced over the past 3 decades, particularly by one of the letter’s authors, Dr. MacGregor. In particular, his mantra has been that sodium content drives beverage consumption.16 That alleged association was recently put to rest by a landmark study in the journal Cell Metabolism.17 The data from the Mars500 study clearly documented dissociation between sodium intake and liquid intake. As with most of Cappuccio et al.’s premises, a direct connection
between the intakes of sodium and fluid is not supported by scientific data.
Disclosure
The authors declared no conflict of interest. References 1. Cappuccio FP, Capewell S, He FH, MacGregor GA. Salt: the dying echoes of the food industry. Am J Hypertens 2013; doi:10.1093/ajh/hpt216. 2. McCarron DA, Kazaks AG, Geerling JC, Stern JS, Graudal NA. Normal range of human dietary sodium intake: 24-hour urinary sodium excretion worldwide. Am J Hypertens 2013; 26:1218–1223. 3. Institute of Medicine. Sodium Intake in Populations: Assessment of Evidence. May 14, 2013. http://www.iom.edu/Reports/2013/ Sodium-Intake-in-Populations-Assessment-ofEvidence.aspx. Accessed 18 November 2013. 4. Oliver WJ, Cohen EL, Neel JV. Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a “no-salt” culture. Circulation 1975; 52:146–151. 5. Kurlansky M. Salt: A World History. Penguin Group: New York, 2003. 6. Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high normal blood pressure. The Trials of Hypertension Prevention, Phase II. Arch Intern Med 1997; 157:657–667. 7. Geerling JC, Loewy AD. Central regulation of sodium appetite. Exp Physiol 2008; 93:177–209. 8. Brunner HR, Laragh JH, Baer L, Newton MA, Goodwin FT, Krakoff LR, Bard RH, Bühler FR. Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 1972; 286:441–449. 9. He FJ, Marciniak M, Visagie E, Markandu ND, Anand V, Dalton RN, MacGregor GA. Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives. Hypertension 2009; 54:482–488. 10. Institute of Medicine. Studies support population-based efforts to lower excessive dietary sodium intakes, but raise questions about potential harm from too little salt intake. http:// www.iom.edu/Reports/2013/Sodium-Intakein-Populations-Assessment-of-Evidence/PressRelease.aspx. Accessed 18 November 2013. 11. Bernstein AM, Willett WC. Trends in 24-hour urinary sodium excretion in the United States, 1957–2003: a systematic review. Am J Clin Nutr 2010; 92:1172–1180. 12. McCarron DA, Geerling JC, Kazaks AG, Stern JS. Can dietary sodium intake be modified by public policy? Clin J Am Soc Nephrol 2009; 4:1878–1882.
American Journal of Hypertension 27(2) February 2014 283
Downloaded from http://ajh.oxfordjournals.org/ at National Chung Hsing University Library on April 12, 2014
sodium reduction on CVD outcomes. This reflects, in part, the fact that virtually all trials of lower sodium have been carried out in “at-risk populations” with little data in normotensive persons representative of the general population. Without such data documenting both the blood pressure and CVD benefit in the healthy, general population, there is no scientific basis for population-wide reduction in sodium intake. Second, the paper by He et al.9 cited by the authors confirms the lower limit of physiologically set sodium intake that our 24-h UNaV data estimated, 115 mmol/day. Their randomized, double-blind study demonstrated a lower limit of 110 mmol/ day, even though the protocol targeted 85 mmol/day for the sodium restriction phase. This finding is also identical to that found in TOHPS II,6 which had the same target of 85 mmol/day but was not able to get lower than 110–115 mmol/ day. These 3 different research designs demonstrate remarkable agreement on the lower limit of sodium intake in freeliving adults. Issue 4. The recent IOM report stands as the definitive analysis.3 Cappuccio et al. know that the findings were based on health outcomes and not the surrogate, blood pressure. The statement regarding the retracted Italian studies is not accurate. The IOM report specifically acknowledged3 the limitation of the Italian congestive heart failure (CHF) studies in addressing the basis of the report’s cautionary note about the potential risk and harm of lower sodium in “at-risk” populations. Given the established opinions supporting sodium reduction that a majority of the panel members10 had expressed in the past, a fact that Cappuccio et al. are certainly aware of, it is even more compelling that the IOM report’s findings failed to support population-wide sodium reduction. Issue 5. The American Journal of Hypertension finding of no change in US sodium intake was indeed initially noted by authors from the Harvard School of Public Health based on 24-h UNaV collections over 5 decades.11 The US 24-h UNaV data cited in our paper were collected from clinical trials primarily funded by the public sector over 50 years and are considered more precise
McCarron et al. 13. Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, Goldman L. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med 2010; 262:590–599. 14. Smith-Spangler CM, Juusola JL, Enns EA, Owens DK, Garber AM. Strategies to decrease sodium intake and the burden of cardiovascular disease. A cost-effectiveness analysis. Ann Intern Med 2010; 152:481–487.
15. Nichols M, Townsend N, Scarborough P, Raynor M. Trends in age-specific coronary heart disease mortality in the European Union over three decades: 1980–2009. Eur Heart J 2013; 34:3017–3027. 16. He FJ, MacGregor GA. A comprehen sive review on salt and health and current experience of worldwide salt reduction programmes. J Hum Hypertens 2009; 23:363–384.
1 7. Rakova N, Jüttner K, Dahlmann A, Schröder A, Linz P, Kopp C, Rauh M, Goller U, Beck L, Agureev A, Vassilieva G, Lenkova L, Johannes B, Wabel P, Moissl U, Vienken J, Gerzer R, Eckardt KU, Müller DN, Kirsch K, Morukov B, Luft FC, Titze J. Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance. Cell Metab 2013; 17:125–131.
Downloaded from http://ajh.oxfordjournals.org/ at National Chung Hsing University Library on April 12, 2014
284 American Journal of Hypertension 27(2) February 2014
Response to “Salt: The Dying Echoes of the Food Industry” David A. McCarron,1 Alexandra G. Kazaks,2 Joel C. Geerling,3 Judith S. Stern,1,4 and Niels A. Graudal5
Correspondence: David A. McCarron ([email protected]). 1Department of Nutrition, University of California at Davis, Davis, California; 2Department of Nutrition and Exercise Science, Bastyr University, Kenmore, Washington; 3Department of Neurology, Beth Israel/ Deaconess Medical Center, Harvard University, Boston, Massachusetts; 4Department of Internal Medicine, University of California at Davis, Davis, California; 5Department of Rheumatology, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Initially submitted November 7, 2013; date of first revision November 12, 2013; accepted for publication November 13, 2013. doi:10.1093/ajh/hpt230 © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: [email protected]
primarily on the controversy regarding the effect of sodium intake reduction on cardiovascular disease (CVD) outcomes. Their basic premise is that “the issue is no longer whether reducing sodium (salt) is of public benefit, it is how best to reduce population salt intake.”1 That statement ignores the principle findings of the recent Institute of Medicine (IOM) report Sodium Intake in Populations,3 which challenged the scientific basis of the current US sodium guidelines. Cappuccio et al. suggest that our scientific data and findings, as well as those of the IOM, by inference, represent an ongoing conspiracy by the food industry that has included “biasing research findings, co-opting policy makers and health professionals, [and] lobbying politicians.” That grandiose hypothesis, by necessity in the case of our data, would mean the food industry manipulated the collections of several hundreds of thousands of 24-h UNaV samples from 69,011 individuals in 45 different countries for more than 5 decades. That allegation is, quite frankly, ludicrous. The opinion-based nature of Cap puccio et al.’s letter is evident in their challenges to the following issues, which they incorrectly characterize as “myths.” Issue 1. They offer no scientific data on the evolution of human sodium intake. Instead they cite the long-touted extrapolation of the very low sodium intake of an isolated primitive society with stunted growth, markedly elevated plasma renin activity (PRA) and aldosterone levels, short lifespan, and a history of extreme violence, including cannibalism.4 They provide no data for their contention that higher sodium intake is “recent” and ignore the clearly established findings in societies spanning several thousand years in which salt was a cornerstone of cultural and economic development.5
282 American Journal of Hypertension 27(2) February 2014
Issue 2. Cappuccio et al. provide no evidence challenging the cited physiological basis of our finding of a “normal range” for human sodium intake. The extensive evidence provided in our AJH paper— including findings from clinical trials6 and the neurosciences,7 the physiology of the relationship between PRA and 24-h UNaV,8 and documentation of the remarkable cultural diversity of 24-h UNaV clearly support the concept of a “normal range.” They offer no plausible, scientific explanation as to how nearly 70,000 people consuming the unique culinary characteristics of 45 countries observed for over 5 decades could possibly excrete sodium within such a narrow range unless it reflects tight physiologic control. Issue 3. The authors question our definition of the lower range of sodium intake. The 115 mmol/day we noted as representing the lower range of normal was defined by standard statistical analysis where 2 standard deviations defined the lower and upper range of the populations’ intake.2 Further, the “classic” PRA/UNaV data portrayed in Figure 3 of our article was derived directly from scientific data published in the New England Journal of Medicine in 1972.8 Published 40 years earlier, that data predicted, within 3 mmol/day, the mean human sodium intake the data in our article2 estimated. The study that Cappuccio et al. cite9 is most interesting not because it showed that modest sodium reduction in white hypertensive persons was associated with a significant increase in PRA, but for 2 other important points they mentioned in their article but not their letter. First, their recognition of the limited demographic variability in trials of sodium restriction is a critical issue. As noted in the IOM report, there is inadequate scientific data on the effects of
Downloaded from http://ajh.oxfordjournals.org/ at National Chung Hsing University Library on April 12, 2014
To the Editor: Cappuccio et al.’s letter, “Salt: The Dying Echoes of the Food Industry,”1 concerning our recent article2 does not address our article’s primary data or its analysis or provide any countervailing scientific data to argue against its interpretation. As our data indicated, “human sodium intake, as defined by 24-hour urinary sodium excretion (24-h UNaV), is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries.” In fact, several of the letter’s authors’ own reports provided scientific data included in our analysis.2 Furthermore, Cappuccio et al. offer no data to refute the decades of clinical and basic research we cited in support of the 24-h UNaV data characterizing a normal distribution of human sodium intake that is determined by appetite-control circuits in the brain, not the food supply. Instead, the authors extensively cite their many prior opinion pieces, none of which offers scientific data relevant to the concept of a “normal range of human sodium intake.” Their letter focuses
Response to Letter to Editor
determinations than food records or recalls used in National Health and Nutrition Examination Surveys (NHANES). The 24-h UNaV data from the other 44 countries describe the same stability even though the individual food supplies likely changed markedly over the timeframe of 5 decades. Issue 6. Cappuccio et al.’s claim of a reduction in the United Kingdom’s sodium intake belies the UK government’s numerous surveys that independent analyses established were simply variation around the mean.11,12 In either case, the change in the UK sodium intake the authors claim (1.5 g of salt or 25 mmol/day), readily falls within the normal range our article described. Cappuccio et al.’s additional claim that sodium reduction accounts for improvements in CVD outcomes is simply untrue, as indicated by the IOM report. The IOM panel based its findings on published data that measured 24-h UNaV and health outcomes over defined periods of time. The panel appropriately rejected, as simply theoretical estimates, the computer models frequently cited by advocates of sodium reduction.13,14 Cappuccio et al.’s claim that policies of sodium reduction in specific countries have been associated with dramatic reduction in CVD mortality is simplistic in its extrapolations. They ignore the reality that recent reports have demonstrated a 50% reduction in CVD death rates between 1980 and 2009 in 26 European countries,15 whereas our data indicate no change in 24-h UNaV in the majority of these same countries. Cappuccio et al. seem to have “cherry picked” examples that fit their argument. Extensive accusatory rhetoric directed at the food industry has been repeatedly voiced over the past 3 decades, particularly by one of the letter’s authors, Dr. MacGregor. In particular, his mantra has been that sodium content drives beverage consumption.16 That alleged association was recently put to rest by a landmark study in the journal Cell Metabolism.17 The data from the Mars500 study clearly documented dissociation between sodium intake and liquid intake. As with most of Cappuccio et al.’s premises, a direct connection
between the intakes of sodium and fluid is not supported by scientific data.
Disclosure
The authors declared no conflict of interest. References 1. Cappuccio FP, Capewell S, He FH, MacGregor GA. Salt: the dying echoes of the food industry. Am J Hypertens 2013; doi:10.1093/ajh/hpt216. 2. McCarron DA, Kazaks AG, Geerling JC, Stern JS, Graudal NA. Normal range of human dietary sodium intake: 24-hour urinary sodium excretion worldwide. Am J Hypertens 2013; 26:1218–1223. 3. Institute of Medicine. Sodium Intake in Populations: Assessment of Evidence. May 14, 2013. http://www.iom.edu/Reports/2013/ Sodium-Intake-in-Populations-Assessment-ofEvidence.aspx. Accessed 18 November 2013. 4. Oliver WJ, Cohen EL, Neel JV. Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a “no-salt” culture. Circulation 1975; 52:146–151. 5. Kurlansky M. Salt: A World History. Penguin Group: New York, 2003. 6. Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high normal blood pressure. The Trials of Hypertension Prevention, Phase II. Arch Intern Med 1997; 157:657–667. 7. Geerling JC, Loewy AD. Central regulation of sodium appetite. Exp Physiol 2008; 93:177–209. 8. Brunner HR, Laragh JH, Baer L, Newton MA, Goodwin FT, Krakoff LR, Bard RH, Bühler FR. Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 1972; 286:441–449. 9. He FJ, Marciniak M, Visagie E, Markandu ND, Anand V, Dalton RN, MacGregor GA. Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives. Hypertension 2009; 54:482–488. 10. Institute of Medicine. Studies support population-based efforts to lower excessive dietary sodium intakes, but raise questions about potential harm from too little salt intake. http:// www.iom.edu/Reports/2013/Sodium-Intakein-Populations-Assessment-of-Evidence/PressRelease.aspx. Accessed 18 November 2013. 11. Bernstein AM, Willett WC. Trends in 24-hour urinary sodium excretion in the United States, 1957–2003: a systematic review. Am J Clin Nutr 2010; 92:1172–1180. 12. McCarron DA, Geerling JC, Kazaks AG, Stern JS. Can dietary sodium intake be modified by public policy? Clin J Am Soc Nephrol 2009; 4:1878–1882.
American Journal of Hypertension 27(2) February 2014 283
Downloaded from http://ajh.oxfordjournals.org/ at National Chung Hsing University Library on April 12, 2014
sodium reduction on CVD outcomes. This reflects, in part, the fact that virtually all trials of lower sodium have been carried out in “at-risk populations” with little data in normotensive persons representative of the general population. Without such data documenting both the blood pressure and CVD benefit in the healthy, general population, there is no scientific basis for population-wide reduction in sodium intake. Second, the paper by He et al.9 cited by the authors confirms the lower limit of physiologically set sodium intake that our 24-h UNaV data estimated, 115 mmol/day. Their randomized, double-blind study demonstrated a lower limit of 110 mmol/ day, even though the protocol targeted 85 mmol/day for the sodium restriction phase. This finding is also identical to that found in TOHPS II,6 which had the same target of 85 mmol/day but was not able to get lower than 110–115 mmol/ day. These 3 different research designs demonstrate remarkable agreement on the lower limit of sodium intake in freeliving adults. Issue 4. The recent IOM report stands as the definitive analysis.3 Cappuccio et al. know that the findings were based on health outcomes and not the surrogate, blood pressure. The statement regarding the retracted Italian studies is not accurate. The IOM report specifically acknowledged3 the limitation of the Italian congestive heart failure (CHF) studies in addressing the basis of the report’s cautionary note about the potential risk and harm of lower sodium in “at-risk” populations. Given the established opinions supporting sodium reduction that a majority of the panel members10 had expressed in the past, a fact that Cappuccio et al. are certainly aware of, it is even more compelling that the IOM report’s findings failed to support population-wide sodium reduction. Issue 5. The American Journal of Hypertension finding of no change in US sodium intake was indeed initially noted by authors from the Harvard School of Public Health based on 24-h UNaV collections over 5 decades.11 The US 24-h UNaV data cited in our paper were collected from clinical trials primarily funded by the public sector over 50 years and are considered more precise
McCarron et al. 13. Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, Goldman L. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med 2010; 262:590–599. 14. Smith-Spangler CM, Juusola JL, Enns EA, Owens DK, Garber AM. Strategies to decrease sodium intake and the burden of cardiovascular disease. A cost-effectiveness analysis. Ann Intern Med 2010; 152:481–487.
15. Nichols M, Townsend N, Scarborough P, Raynor M. Trends in age-specific coronary heart disease mortality in the European Union over three decades: 1980–2009. Eur Heart J 2013; 34:3017–3027. 16. He FJ, MacGregor GA. A comprehen sive review on salt and health and current experience of worldwide salt reduction programmes. J Hum Hypertens 2009; 23:363–384.
1 7. Rakova N, Jüttner K, Dahlmann A, Schröder A, Linz P, Kopp C, Rauh M, Goller U, Beck L, Agureev A, Vassilieva G, Lenkova L, Johannes B, Wabel P, Moissl U, Vienken J, Gerzer R, Eckardt KU, Müller DN, Kirsch K, Morukov B, Luft FC, Titze J. Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance. Cell Metab 2013; 17:125–131.
Downloaded from http://ajh.oxfordjournals.org/ at National Chung Hsing University Library on April 12, 2014
284 American Journal of Hypertension 27(2) February 2014
