Impact of Sugar-Sweetened Beverages on Blood Pressure

Aaqib Habib Malik, MD, BSc, MPHa,b,*, Yasir Akram, MD, MPHa, Suchith Shetty, MD, MPHa,Senada Senda Malik, MPH, BScc, and Valentine Yanchou Njike, MD, MPHb

The impact of sugar-sweetened beverages (SSBs) on blood pressure (BP) has been debated,

aDepartment oDerby, ConnecticConnecticut; and c

Portland, Maine. Mscript received and

See page 1578*CorrespondinE-mail addres

0002-9149/14/$ -http://dx.doi.org/1

with some evidence suggesting that their increased intake is related to higher risk ofdeveloping hypertension. We conducted a systematic review exploring the relation betweenconsumption of SSB and BP. A comprehensive search in 5 electronic databases along with abibliography search was performed. The keywords “sugar sweetened beverages,” “sugarydrinks,” “added sugars,” “blood pressure,” and “hypertension” were indexed in all com-binations. Studies were included that reported the effects of intake of SSBs on BP. Weexcluded studies with <100 subjects and those involving subjects aged <12 years. Of 605potentially relevant studies, a total of 12 studies (409,707 participants) met our inclusioncriteria; 6 were cross sectional studies, whereas the rest were prospective cohort studies. All12 studies showed positive relation between increased SSB intake and hypertension; how-ever, statistical significance was reported in 10 of these studies. Of the 12 studies, 5 reportedan increase in mean BP whereas 7 reported an increase in the incidence of high BP. Inconclusion, our systematic review shows that the consumption of SSBs is associated withhigher BP, leading to increased incidence of hypertension. Restriction on SSB consumptionshould be incorporated in the recommendations of lifestyle modifications for the treatment ofhypertension. Interventions to reduce intake of SSBs should be an integral part of publichealth strategy to reduce the incidence of hypertension. � 2014 Elsevier Inc. All rightsreserved. (Am J Cardiol 2014;113:1574e1580)

Sugar-sweetened beverages (SSBs) are the largest sourceof added sugar in our diet. They include any beverage towhich a caloric sweetener has been added. In the UnitedStates, high-fructose corn syrup (HFCS) is themajor source ofadded sweeteners in sweetened beverages.1,2 There has been a40% increase in HFCS consumption over the last 30 years,which is higher than any other food product.3 In the year 2000,42% of added sugar in food products was in the form ofHFCS. On an average day, 67% of adults and 4 in 5 adoles-cents consume SSBs in the United States.4,5 A recent reportpresented at an American Heart Association meeting impli-cated 180,000 deaths/year to consumption of SSBs.6 TheAmerican Heart Association recommends consumption of nomore than 450 calories/week from SSBs.6 SSBs and theirimpact on health have been extensively studied over the last15 years. Consumption of SSBs has been shown to cause anincreased risk of obesity,metabolic syndrome, type 2 diabetesmellitus, heart disease, gout, and kidney stones.7e11 Recentmeta-analyses have confirmed these findings by showing thatSSBs are associated with a 26% increased risk of diabetesmellitus and a 20% increased risk of metabolic syndrome.7,12

To date, no systematic review has been done to summarize thestudies that examined the effects of SSBs on blood pressure

f Internal and Preventive Medicine, Griffin Hospital,ut; bYale-Griffin Prevention Research Center, Derby,Department of Public Health, University of New England,anuscript received November 4, 2013; revised manu-accepted January 20, 2014.for disclosure information.g author: Tel: (203) 732-1265; fax: (203) 732-1264.s: aaqib2012@aya.yale.edu (A.H. Malik).

see front matter � 2014 Elsevier Inc. All rights reserved.0.1016/j.amjcard.2014.01.437

(BP). The objective of our review is to summarize the studiesevaluating the relation between SSBs and BP.

Methods

WesearchedMEDLINE,MEDLINE In-Process andOtherNon-Indexed Citations, EMBASE, Allied and Complemen-tary Medicine Database, and PsycINFO to identify all therelevant studies up to August 2013. The detailed searchstrategy is explained in the Appendix. The keywords “sugarsweetened beverages,” “sugary drinks,” “added sugars,”“blood pressure,” and “hypertension” were indexed in allcombinations for original reports and clinical studiesincluding cross-sectional studies, observational studies,clinical trial studies, and reviews. These reports were evalu-ated against an a priori inclusion and exclusion criteria.Additionally, we checked reference lists of other publishedreviews and relevant reports to identify any additional studies.We limited our search to “human studies” and “English lan-guage articles.” Two independent reviewers examined titles,abstracts, and full reports for eligibility. We resolved dis-crepancies by mutual discussion and consensus.

All the studies that measured and reported the effects ofSSBs onBP or on the incidence of hypertensionwere included.We looked at studies involving subjects aged �12 years. Weexcluded studies that did not specifically mention the effects ofSSBs on BP, studies involving children aged <12 years, andstudies with <100 participants.13e21

We extracted the details on study design and methods,sample size, beverage category, and final outcome on BP.Quality assessment of the studies was conducted by 2 inde-pendent reviewers using the Newcastle-Ottawa Scale forobservational studies as a guide.22 The quality of the studies

www.ajconline.org

Figure 1. Preferred reporting items for systematic reviews and meta-analyses diagram.

Review/Sugar-Sweetened Beverages and Blood Pressure 1575

was further evaluated for selection, attrition, performance,detection, and reporting biases.Afinal quality grade fromA toC was assigned to each study. We resolved discrepancies inquality rating grades by discussion and mutual consensus.

Results

We identified a total of 918 reports in electronic databases.A manual search performed through the reference lists ofrelevant reviews and reports yielded 7 additional studies.Detailed schema is explained in preferred reporting items forsystematic reviews and meta-analyses diagram (Figure 1).After deduplication and title and abstract screening of 605reports, we retrieved 21 potential full-text reports for in-depthevaluation. On full-text review 9 of these articles wereexcluded for various reasons as mentioned in Figure 1.

The final 12 studies consisted of 6 cross-sectional and6 prospective analyses of observational cohort studies. Noneof the studies showed a beneficial effect on BP from SSBconsumption. In this review, 10 of the 12 studies showed apositive relation between increased SSB intake and high BP.

The other 2 studies, although showing a positive trend, failedto show an association at a statistical level. These effects areillustrated in Figures 2 and 3. Figure 2 depicts 7 studies thatshow that increased consumption of SSBs is associated withhigher odds of increased incidence of hypertension.Figure 3illustrates 5 studies showing an average increase in systolicblood pressure (SBP) with increased SSB consumption.

Table 1 summarizes the cross-sectional studies showingassociation between SSBs and hypertension. The overallrelation between consumption of SSB and BP is positive. All6 studies employed interviewer-administered recall-basedstructured food frequency questionnaires for dietary assess-ment. Three studies reported that the odds of becominghypertensive range from 26% to 70% with increased con-sumptionofSSBs.23e25Theother 3 studies reported increase inthemeanBP. They found 0.16- to 1.6-mmHg increase inmeanSBP with increased SSB intake.26e28 Four of 6 studiesinvolved theUSpopulation, as theywere based on theNationalHealth andNutrition Examination Survey (NHANES).23,25e27

Cross-sectional analysis of these surveys showed a positiveassociation of SSB intake with incident hypertension. Nguyen

Figure 3. Mean increase in SBP with increased SSB consumption.

Figure 2. Odds ratio of incidence of hypertension with increased SSB consumption.

1576 The American Journal of Cardiology (www.ajconline.org)

et al26 in 2009 and Kim et al25 in 2012 used NHANES datafrom different years (1999 to 2004 and 2003 to 2006) fordifferent age groups, 12 to 18 years and �19 years, respec-tively, and came to similar conclusions. In amultivariatemodelof a relatively younger cohort, Kim et al25 concluded thatadolescents who consumed SSBs �3 times/day had an 87%increased risk of becoming hypertensive. Nguyen et al26

reported a mean increase of 0.17 mm Hg of SBP in subjectswho consumed >36 fl oz of SSBs per day. Similarly, Jalalet al23 in 2010 and Bremer et al27 in 2009 used the exact sameNHANES data as previously was done by Nguyen et al26 andKim et al,25 respectively. In addition, they added 1 extra year intheir inclusion criteria. They used �18 years instead of�19 years for NHANES 1999 to 2004 and 12 to 19 yearsinstead of 12 to 18 years for NHANES 2003 to 2006. Asexpected, Jalal et al23 concluded that consumption of 2.5 sug-ary soft drinksper day is independently associatedwith ahigherrisk of having increased SBP, whereas Bremer et al27 showedthat each additional SSB serving (8fl oz) resulted in an increasein SBP of 0.16 mm Hg (p <0.05). Later, the multicenterInternational Study of Macro and Micronutrients and BloodPressure (INTERMAP) study confirmed these findings by

showing that increased SSB intake of 1 serving (12 fl oz) wasassociated with 1.6-mm Hg increase in SBP.28

Table 2 summarizes the prospective studies showingassociation of SSB intake and incidence of hypertension.Five of 6 cohort studies represented the US population, and1 prospective analysis was performed in Australia. Dietaryassessment was performed by way of food frequency ques-tionnaires implemented at various times during the studies.There was an overall positive trend of having higher BP withincreased intake of SSBs. Two studies reported mean BPdifference and showed 1.8- and 1.9-mm Hg increases inaverage SBP with increased consumption of SSBs (>1serving/day).29,30 This is in conformity with the conclusionby the INTERMAP study investigators. Three studies of 6reported an increase in the incidence of hypertension withincreased consumption of SSBs, with an odds ratio range of1.13 to 1.6.31e33 The only conflicting data come from astudy by Ambrosini et al,30 of a much younger cohort, whichshowed no difference in BP after multivariate adjustment.Moreover, Dhingra et al31 in their Framingham OffspringStudy also showed only a marginal increase in the incidenceof hypertension with >1 serving/day of a 12-fl oz SSB

Table 2Summary of prospective studies

Study Population Sample Size Age (yrs) Sweetener Used Statistical Test/Model Used

ConfounderAdjustment*

Grade

Chen et al29 PREMIER study 810 25e79 HFCS Mixed-effects models Yes BAmbrosini et al30 Australian offspring

cohort1,433 14e17 Not mentioned Longitudinal (mixed-

effects) modelsYes B

Dhingra et al31 Framingham offspringcohort

2,803 42e66 HFCS Multiple logisticregression

Yes B

Winkelmayer et al32 2 cohorts (NHS I andNHS II)

155,594 25e55 HFCS Multivariate adjustedregression

Yes B

Duffey et al33 CARDIA cohort 2,774 18e30 HFCS Multivariable-adjustedregression

Yes B

Cohen et al34 3 cohorts (NHS I,NHS II, and HPFS)

223,891 25e75 HFCS Multivariate adjustedregression

Yes B

CARDIA ¼ Coronary Artery Risk Development in Young Adults; NHS ¼ Nurses’ Health Study.* Confounder adjustment performed for analysis.

Table 1Summary of cross-sectional studies

Study Population (yr) Sample Size Age (yrs) Sweetener Used DietaryAssessment

Statistical Test/Model Used

ConfounderAdjustment*

Grade

Jalal et al23 NHANES (2003e2006)

4,528 �18 HFCS Interviewer-administeredrecall-based FFQ

Univariate modeling Yes B

Tayel et al24 School children inEgypt (2013)

300 12e18 Not mentioned Interviewer-administeredrecall-based FFQ

Stepwise linearregression

No C

Kim et al25 NHANES (2003e2006)

3,044 �19 HFCS Interviewer-administeredrecall-based FFQ

Multivariate logisticregression

Yes B

Nguyen et al26 NHANES (1999e2004)

4,867 12e18 HFCS Interviewer-administeredrecall-based FFQ

Multivariate linearregression

Yes B

Bremer et al27 NHANES (1999e2004)

6,967 12e19 HFCS Interviewer-administeredrecall-based FFQ

Multivariate linearregression

Yes B

Brown et al28 INTERMAP (1996e1999)

2,696 40e59 HFCS, glucose,and sucrose

Interviewer-administeredrecall-based FFQ

Multiple regressionanalyses

Yes B

FFQ ¼ food frequency questionnaire.* Confounder adjustment performed for cross-sectional analysis.

Review/Sugar-Sweetened Beverages and Blood Pressure 1577

(odds ratio 1.18, 95% confidence interval 0.96 to 1.44). Themost noteworthy positive evidence in a prospective studycomes from Chen et al29 who, in an 18-month long, multi-center, behavioral, randomized controlled trial, showed areduction of 1.8 mm Hg of SBP and 1.1 mm Hg of diastolicBP by reducing 0.9 servings/day (10.5 fl oz) of SSBs.Coronary Artery Risk Development in Young Adults(CARDIA) study results attribute SSBs to be responsible fora 6% increase in the risk of hypertension33; Cohen et al34

displayed a 6% to 20% increase in the incidence of hyper-tension per 12 fl oz of SSBs. Similarly, Winkelmayer et al32

showed 28% to 44 % increased risk of developing hyper-tension with increased SSB intake. The age range of thesecohorts was 14 to 75 years with the length of follow-upspanning 18 months to 38 years. This suggests that positiveassociation between increased SSB intake and hypertension

is independent of age and becomes significantly greater after18 months of increased consumption of SSBs.

Discussion

Overall, noneof the studies showedabeneficial effect onBPfrom SSB consumption. In general, even by the most conser-vative estimate, intake of>12fl oz of SSB per day can increasethe risk of having hypertension by at least 6%, and it canincrease mean SBP by a minimum of 1.8 mm Hg in roughlyover 18 months. This can be very significant at a populationlevel. In the past, a modest reduction in SBP at a populationlevel has been proven to translate into substantial reductions indeaths from stroke and coronary heart disease. On average, a2-mm Hg reduction in SBP is expected to reduce deaths fromstroke by 10%,whereas a similar reduction in diastolic BPmay

1578 The American Journal of Cardiology (www.ajconline.org)

account for a 17% reduction in prevalence of hypertension, 6%reduction in coronary heart disease, and a 15% reduction instroke.5,11,35e38 The results from the PREMIER study showedthat the reduction inBPwas foundnot only in the normotensivebut also in the hypertensive population. Consequently, theseresults are generalizable to the adult population, includingdiseased, prehypertensive, and normotensive subjects. Threestudies byAmbrosini et al,30 Bremer et al,27 andNguyen et al26

evaluated effects of SSBs on adolescent population aged 12 to18 years. They showed amuch reduced effect on BP comparedwith the studies done in older population. This may be becauseeffects on vessels could be different during adolescence.

Generally, the NHANES andNurses’Health Study (NHS)cohorts used in this analysis are relatively large and the mainbenefit of using these cohorts is that they are representative ofa large community, and, therefore, the results are generaliz-able to a much larger adult population. Also, most studiesadjusted for potential confounders in their analyses, includingdemographics and lifestyle factors. Additionally, to counter along follow-up period and potential change of diet in suchperiods, most studies conducted the dietary assessment every2 years.

SSBs in the United States often contain HFCS, which in thepast has been implicated in high BP. It is primarily thought tocause obesity and metabolic syndrome and secondarily canraise BP.39 The most widely known mechanism for HFCS tocause high BP involves an increase in uric acid production,which in turn results in lowering of nitric oxide in the body. Asmall study showed that consumption of >500 ml/day ofHFCS-containing beverages confers 2 times increased risk ofdeveloping hyperuricemia.40 Nitric oxide is a vasodilator andits relative reduction can result in high BP.41e44 Other theoriesbehind high SSB intake being implicated in hypertensioninvolve decreased sodium excretion or activation of the sym-pathetic nervous system.45,46 Additionally, it can also increasethe sodium concentration in the body through increased gutabsorption.47 Another theory involves a model based on fluidentrapment in the small bowel, leading to sodium retention.48 Ithas been shown previously that unhealthy lifestyle behaviorsand increased sugar consumption go hand in hand withincreased salt consumption, and that this in effect can lead tohigher BP.49,50 These findings are validated by a recent studyby Grimes et al,51 which showed that 17 grams of increasedSSB intake is associated with each additional gram of saltintake in 1 day. A recent study of middle-aged twins byEufinger et al52 showed reduction in coronaryflow reservewithincreased consumption of SSBs. This could be an interestingfinding for future studies evaluating the effects of SSBson cardiovascular morbidity and mortality. Another study bySanchez-Lozada et al42 showed that fructose can causemetabolic syndrome through renal hypertrophy, glomerularhypertension, and cortical vasoconstriction. Furthermore, arandomized controlled trial of a low-fructose diet resulted inreduction in BP and inflammation in patients with chronickidney disease, whereas another randomized controlled trialshowed that fructose can raise BP acutely.19,53 In anotherindependent study of 59,334 Danish pregnant women, artifi-cially sweetened carbonated and noncarbonated soft drinks of>1 serving/day increased the risk of preterm delivery by 38%and20%, respectively.54Higher pretermdeliveries in this studywere driven by medically induced deliveries, which suggests

that these deliveries might have been due to hypertensive dis-orders and endothelial dysfunctions associated with them,hence linkingHFCS intake and hypertension. Further evidencecomes from a Norwegian study showing increased risk ofeclampsia with maternal SSB intake.55 In 2009, Forman et al13

used cohorts of NHS I and II and Health Professionals Follow-up Study and failed to show an association between totalfructose intake and hypertension. This could be explained bythe fact that theycalculated total fructose intake, andmostof thefructose intake was in the natural form of fruits. This argumentis strengthened by the fact that the same cohort produced sig-nificant association with hypertension when fructose contentfrom natural fruits was excluded from analysis.34

It remains unclear at what dose increased SSB intake leadsto development of hypertension. On the basis of these studies,although, there is a suggestion that intake of >1 serving ofSSB per day is associated with higher risk of hypertension. Astudy by the Harvard School of Public Health showed thatSSBs account for 25,000 deaths/year, which is equivalent to8.1/100,000 deaths, in the United States.5 This is higher thanthe death rate attributed to homicide, AIDS, alcohol, drug use,and certain cancers (leukemia, cervical cancer, skin cancer,and so forth), individually. Most of these deaths due to SSBare reported in amuch younger population (<45 years), whichis considered to be the most productive age group.6,56 Thisleads us to the conclusion that persistent long-term con-sumption of SSBs might lead to the development of hyper-tension and eventual cardiovascular events.

The major limitations of this review are a lack of randomi-zation and the observational nature of included studies. Wecannot link causality on basis of these observations, althoughthey are highly suggestive of the risk. Despite controlling forconfounders, there is a potential for residual confounding. It isplausible that subjects who drinkmore SSBs are less cognizantof their health status and therefore are involved in lifestyle andother dietary practices that may increase their BP.57 Addi-tionally, most of the prospective cohort studies used validatedsemiquantitative food frequency questionnaires to assessdietary intake. Although it is a valuable tool for observationalstudies, these recall-based dietary assessment methods areoften unreliable and prone to bias.58 However, the errorscreated because of these somewhat inaccurate questionnairesare likely to be nondifferential, thus driving the bias toward thenull. Moreover, subjects tend to underreport unhealthybehaviors, which in fact might diminish the observed effect ofSSBs on BP, rendering these results more valid.59 Finally, weshould bear in mind the risk of publication bias, as these largestudies showing significant findings are more likely to getpublished.

Disclosures

The authors have no conflicts of interest to disclose.

Supplementary Data

Supplementary data associated with this article can befound, in the online version, at http://dx.doi.org/10.1016/j.amjcard.2014.01.437.

1. Vuilleumier S. Worldwide production of high-fructose syrup andcrystalline fructose. Am J Clin Nutr 1993;58:S733eS736.

Review/Sugar-Sweetened Beverages and Blood Pressure 1579

2. Rebollo A, Roglans N, Alegret M, Laguna JC. Way back for fructoseand liver metabolism: bench side to molecular insights. World J Gas-troenterol 2012;18:6552e6559.

3. Havel PJ. Dietary fructose: implications for dysregulation of energyhomeostasis and lipid/carbohydrate metabolism. Nutr Rev 2005;63:133e157.

4. Bleich SN, Wang YC, Wang Y, Gortmaker SL. Increasing consump-tion of sugar-sweetened beverages among US adults: 1988-1994 to1999-2004. Am J Clin Nutr 2009;89:372e381.

5. Wang YC, Bleich SN, Gortmaker SL. Increasing caloric contributionfrom sugar-sweetened beverages and 100% fruit juices among US chil-dren and adolescents, 1988-2004. Pediatrics 2008;121:e1604ee1614.

6. Singh GM, Micha R, Katibzadeh S, Lim S, Ezzati M, Mozaffarian D.Mortality due to sugar-sweetened beverage consumption: a global,regional, and national comparative risk assessment.Circulation 2013;127:AMP22.

7. Malik VS, Popkin BM, Bray GA, Despres JP, Willett WC, Hu FB.Sugar-sweetened beverages and risk of metabolic syndrome and type 2diabetes: a meta-analysis. Diabetes Care 2010;33:2477e2483.

8. Schulze MB, Manson JE, Ludwig DS, Colditz GA, Stampfer MJ,Willett WC, Hu FB. Sugar-sweetened beverages, weight gain, andincidence of type 2 diabetes in young and middle-aged women. JAMA2004;292:927e934.

9. Fung TT, Malik V, Rexrode KM, Manson JE, Willett WC, Hu FB.Sweetened beverage consumption and risk of coronary heart disease inwomen. Am J Clin Nutr 2009;89:1037e1042.

10. Choi HK, Willett W, Curhan G. Fructose-rich beverages and risk ofgout in women. JAMA 2010;304:2270e2278.

11. Malik VS, Schulze MB, Hu FB. Intake of sugar-sweetened beveragesand weight gain: a systematic review. Am J Clin Nutr 2006;84:274e288.

12. Vartanian LR, Schwartz MB, Brownell KD. Effects of soft drinkconsumption on nutrition and health: a systematic review and meta-analysis. Am J Public Health 2007;97:667e675.

13. Forman JP, Choi H, Curhan GC. Fructose and vitamin C intake do notinfluence risk for developing hypertension. J Am Soc Nephrol 2009;20:863e871.

14. Madero M, Arriaga JC, Jalal D, Rivard C, McFann K, Perez-MendezO, Vazquez A, Ruiz A, Lanaspa MA, Jimenez CR, Johnson RJ, LozadaLG. The effect of two energy-restricted diets, a low-fructose diet versusa moderate natural fructose diet, on weight loss and metabolic syn-drome parameters: a randomized controlled trial. Metabolism 2011;60:1551e1559.

15. Lowndes J, Kawiecki D, Pardo S, Nguyen V, Melanson KJ, Yu Z,Rippe JM. The effects of four hypocaloric diets containing differentlevels of sucrose or high fructose corn syrup on weight loss and relatedparameters. Nutr J 2012;11:55.

16. Mark S, Wang J, Gray-Donald K, Henderson M, O’Loughlin J,Tremblay A, Lambert M. Sugar-sweetened beverage intake andmetabolic syndrome components among children at high risk ofobesity. Can J Diabetes 2011;35:142.

17. Perichart-Perera O, Balas-Nakash M, Rodriguez-Cano A, Munoz-Manrique C, Monge-Urrea A, Vadillo-Ortega F. Correlates of dietaryenergy sources with cardiovascular disease risk markers in Mexicanschool-age children. J Am Diet Assoc 2010;110:253e260.

18. Shang XW, Liu AL, Zhang Q, Hu XQ, Du SM, Ma J, Xu GF, Li Y,Guo HW, Du L, Li TY, Ma GS. Report on childhood obesity in China(9): sugar-sweetened beverages consumption and obesity. BiomedEnviron Sci 2012;25:125e132.

19. Brown CM, Dulloo AG, Yepuri G, Montani JP. Fructose ingestionacutely elevates blood pressure in healthy young humans. Am J PhysiolRegul Integr Comp Physiol 2008;294:R730eR737.

20. Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, ChabanovaE, Thomsen H, Pedersen SB, Astrup A, Richelsen B. Sucrose-sweet-ened beverages increase fat storage in the liver, muscle, and visceral fatdepot: a 6-mo randomized intervention study. Am J Clin Nutr 2012;95:283e289.

21. Le MT, Frye RF, Rivard CJ, Cheng J, McFann KK, Segal MS, JohnsonRJ, Johnson JA. Effects of high-fructose corn syrup and sucrose on thepharmacokinetics of fructose and acute metabolic and hemodynamicresponses in healthy subjects. Metabolism 2012;61:641e651.

22. WellsG, SheaB,O’connell D, Peterson J,WelchV, LososM, Tugwell P.The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analyses. Available at:http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed Jan 15, 2014.

23. Jalal DI, Smits G, Johnson RJ, Chonchol M. Increased fructose asso-ciates with elevated blood pressure. J Am Soc Nephrol 2010;21:1543e1549.

24. Tayel DI, El-Sayed NA, El-Sayed NA. Dietary pattern and bloodpressure levels of adolescents in Sohag, Egypt. J Egypt Public HealthAssoc 2013;88:97e103.

25. Kim YH, Abris GP, Sung MK, Lee JE. Consumption of sugar-sweetened beverages and blood pressure in the United States: theNational Health and Nutrition Examination Survey 2003-2006. ClinNutr Res 2012;1:85e93.

26. Nguyen S, Choi HK, Lustig RH, Hsu CY. Sugar-sweetened beverages,serum uric acid, and blood pressure in adolescents. J Pediatr 2009;154:807e813.

27. Bremer AA, Auinger P, Byrd RS. Relationship between insulin resis-tance-associated metabolic parameters and anthropometric measure-ments with sugar-sweetened beverage intake and physical activitylevels in US adolescents: findings from the 1999-2004 National Healthand Nutrition Examination Survey. Arch Pediat Adolesc Med2009;163:328e335.

28. Brown IJ, Stamler J, Van Horn L, Robertson CE, Chan Q, Dyer AR,Huang CC, Rodriguez BL, Zhao L, Daviglus ML, Ueshima H, Elliott P;International Study of Macro/Micronutrients and Blood PressureResearch Group. Sugar-sweetened beverage, sugar intake of individuals,and their blood pressure: International Study of Macro/Micronutrientsand Blood Pressure. Hypertension 2011;57:695e701.

29. Chen L, Caballero B, Mitchell DC, Loria C, Lin PH, Champagne CM,Elmer PJ, Ard JD, Batch BC, Anderson CA, Appel LJ. Reducingconsumption of sugar-sweetened beverages is associated with reducedblood pressure: a prospective study among United States adults.Circulation 2010;121:2398e2406.

30. Ambrosini GL, Oddy WH, Huang RC, Mori TA, Beilin LJ, Jebb SA.Prospective associations between sugar-sweetened beverage intakes andcardiometabolic risk factors in adolescents. Am J Clin Nutr 2013;98:327e334.

31. Dhingra R, Sullivan L, Jacques PF, Wang TJ, Fox CS, Meigs JB,D’Agostino RB, Gaziano JM, Vasan RS. Soft drink consumption andrisk of developing cardiometabolic risk factors and the metabolic syn-drome in middle-aged adults in the community. Circulation 2007;116:480e488.

32. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitualcaffeine intake and the risk of hypertension in women. JAMA2005;294:2330e2335.

33. Duffey KJ, Gordon-Larsen P, Steffen LM, Jacobs DR Jr, Popkin BM.Drinking caloric beverages increases the risk of adverse cardiometabolicoutcomes in the Coronary Artery Risk Development in Young Adults(CARDIA) Study. Am J Clin Nutr 2010;92:954e959.

34. Cohen L, Curhan G, Forman J. Association of sweetened beverageintake with incident hypertension. J Gen Intern Med 2012;27:1127e1134.

35. Reedy J, Krebs-Smith SM. Dietary sources of energy, solid fats, andadded sugars among children and adolescents in the United States.J Am Diet Assoc 2010;110:1477e1484.

36. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specificrelevance of usual blood pressure to vascular mortality: a meta-analysisof individual data for one million adults in 61 prospective studies.Lancet 2002;360:1903e1913.

37. Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE,Giles WH, Capewell S. Explaining the decrease in U.S. deaths fromcoronary disease, 1980-2000. N Engl J Med 2007;356:2388e2398.

38. Cook NR, Cohen J, Hebert PR, Taylor JO, Hennekens CH. Implica-tions of small reductions in diastolic blood pressure for primary pre-vention. Arch Intern Med 1995;155:701e709.

39. Brownell KD, Frieden TR.Ounces of prevention—the public policy casefor taxes on sugared beverages. N Engl J Med 2009;360:1805e1808.

40. Lin WT, Huang HL, Huang MC, Chan TF, Ciou SY, Lee CY, ChiuYW, Duh TH, Lin PL, Wang TN, Liu TY, Lee CH. Effects on uricacid, body mass index and blood pressure in adolescents of consumingbeverages sweetened with high-fructose corn syrup. Int J Obes (Lond)2013;37:532e539.

41. Lustig RH. Fructose: metabolic, hedonic, and societal parallels withethanol. J Am Diet Assoc 2010;110:1307e1321.

42. Sanchez-Lozada LG, Tapia E, Jimenez A, Bautista P, Cristobal M,Nepomuceno T, Soto V, Avila-Casado C, Nakagawa T, Johnson RJ,Herrera-Acosta J, Franco M. Fructose-induced metabolic syndrome is

1580 The American Journal of Cardiology (www.ajconline.org)

associated with glomerular hypertension and renal microvasculardamage in rats. Am J Physiol Ren Physiol 2007;292:F423eF429.

43. Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O,Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, JohnsonRJ. A causal role for uric acid in fructose-induced metabolic syndrome.Am J Physiol Ren Physiol 2006;290:F625eF631.

44. Perez-Pozo SE, Schold J, Nakagawa T, Sanchez-Lozada LG, JohnsonRJ, Lillo JL. Excessive fructose intake induces the features of meta-bolic syndrome in healthy adult men: role of uric acid in the hyper-tensive response. Int J Obes (Lond) 2010;34:454e461.

45. Brito JO, Ponciano K, Figueroa D, Bernardes N, Sanches IC, IrigoyenMC, De Angelis K. Parasympathetic dysfunction is associated withinsulin resistance in fructose-fed female rats. Braz J Med Biol Res2008;41:804e808.

46. Rebello T, Hodges RE, Smith JL. Short-term effects of various sugarson antinatriuresis and blood pressure changes in normotensive youngmen. Am J Clin Nutr 1983;38:84e94.

47. Singh AK, Amlal H, Haas PJ, Dringenberg U, Fussell S, Barone SL,Engelhardt R, Zuo J, Seidler U, Soleimani M. Fructose-inducedhypertension: essential role of chloride and fructose absorbing trans-porters PAT1 and Glut5. Kidney Int 2008;74:438e447.

48. Kurbel S. Arterial hypertension due to fructose ingestion: model basedon intermittent osmotic fluid trapping in the small bowel. Theor BiolMed Model 2010;7:27.

49. Feig DI, Mazzali M, Kang DH, Nakagawa T, Price K, Kannelis J,Johnson RJ. Serum uric acid: a risk factor and a target for treatment?J Am Soc Nephrol 2006;17:S69eS73.

50. He FJ, Marrero NM, MacGregor GA. Salt intake is related to soft drinkconsumption in children and adolescents: a link to obesity? Hyper-tension 2008;51:629e634.

51. Grimes CA, Riddell LJ, Campbell KJ, Nowson CA. Dietary salt intake,sugar-sweetened beverage consumption, and obesity risk. Pediatrics2013;131:14e21.

52. Eufinger SC, Votaw J, Faber T, Ziegler TR, Goldberg J, Bremner JD,Vaccarino V. Habitual dietary sodium intake is inversely associatedwith coronary flow reserve in middle-aged male twins. Am J Clin Nutr2013;95:572e579.

53. BrymoraA, FlisinskiM, JohnsonRJ, GoszkaG, StefanskaA,Manitius J.Low-fructose diet lowers blood pressure and inflammation in patientswith chronic kidney disease. Nephrol Dial Transpl 2012;27:608e612.

54. Halldorsson TI, Strom M, Petersen SB, Olsen SF. Intake of artificiallysweetened soft drinks and risk of preterm delivery: a prospective cohortstudy in 59,334 Danish pregnant women. Am J Clin Nutr 2010;92:626e633.

55. Borgen I, Aamodt G, Harsem N, Haugen M, Meltzer HM, BrantsaeterAL. Maternal sugar consumption and risk of preeclampsia in nullipa-rous Norwegian women. Eur J Clin Nutr 2012;66:920e925.

56. USA causes of death by age and gender; CDC Official Final Deaths2010. Available at: http://www.worldlifeexpectancy.com/usa-cause-of-death-by-age-and-gender. Accessed January 15, 2014.

57. Forman JP, Stampfer MJ, Curhan GC. Diet and lifestyle risk factorsassociated with incident hypertension in women. JAMA 2009;302:401e411.

58. Ambrosini GL, de Klerk NH, O’Sullivan TA, Beilin LJ, Oddy WH.The reliability of a food frequency questionnaire for use amongadolescents. Eur J Clin Nutr 2009;63:1251e1259.

59. Emond JA, Patterson RE, Jardack PM, Arab L. Using doubly labeledwater to validate associations between sugar-sweetened beverageintake and body mass among White and African-American adults. Int JObes (Lond) 2013.