Cardiovascular Topics

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1 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA Advnce Online Publiction, Februry Crdiovsculr Topics Obesity msks the reltionship between dietry slt intke nd blood pressure in people of Africn ncestry: the impct of obesity on the reltionship between sodium nd blood pressure Muzi Mseko, Mercy Msho, Abdulrheem Bw-Allh, Edgr Phukubje, Bongubuhle Mlmbo, Thmsnq Nyundu Abstrct Previous studies conducted to investigte the reltionship between sodium intke nd blood pressure in our Africn popultion hve yielded contrdictory results. With the high prevlence of obesity in this popultion, it is possible tht these contrdictory findings re due to the msking effects of obesity on this reltionship. We mesured 24-hour mbultory blood pressure nd 24-hour urine excretion on 547 South Africns of Africn ncestry. A multivrite regression nlysis reveled no independent reltionship between 24-hour sodium excretion nd blood pressure in the totl popultion smple, but when prticipnts were strtified ccording to body mss index (BMI) sttus, there ws significnt ssocition between 24-hour sodium excretion nd blood pressure in the norml-bmi prticipnts but not in the overweight/obese prticipnts. We concluded tht dietry slt intke, indexed by 24-hour urinry sodium excretion, ws ssocited with incresed mbultory blood pressure but this reltionship ws msked becuse of high proportion of overweight/obese individuls in this popultion. Keywords: dietry slt intke, obesity, hypertension, slt retention, body mss index Submitted 24/3/17, ccepted 29/1/18 Crdiovsc J Afr 2018; 29: online publiction DOI: /CVJA Crdiovsculr diseses (CVD) re presently leding cuse of deth in South Afric nd sub-shrn Afric (SSA). 1,2 School of Physiology, Fculty of Helth Sciences, University of the Witwtersrnd, Johnnesburg, South Afric Muzi Mseko, PhD, muzi.mseko@wits.c.z Mercy Msho, MSc Abdulrheem Bw-Allh, MSc Edgr Phukubje, BSc Bongubuhle Mlmbo, BSc Thmsnq Nyundu, MSc Hypertension remins the commonest risk fctor for CVD. 3,4 A number of studies hve ssocited n incresed dietry sodium (N + ) intke nd obesity with hypertension nd trget-orgn dmge. 5 In n effort to lessen the worldwide prevlence of hypertension, globl strtegies nd popultion-bsed intervention studies, including Dietry Approches to Stop Hypertension (DASH), hve focused prticulrly on reduction of N + intke s mens of lowering blood pressure (BP) in popultion. 6-8 This could be of benefit to people of Africn descent becuse number of studies hve shown tht the incidence of hypertension is incresing in blck communities However there is gp in our knowledge on the role of dietry sodium on blood pressure in this community. Even though previous studies conducted in this popultion hve reveled high prevlence of hypertension, 12,13 the reltionship between dietry slt intke nd BP is still not well understood becuse studies hve reveled contrdictory findings on this reltionship. 14,15 One study showed modest ssocition, 16 while others showed no ssocition. 17,8 In one study, the investigtors showed n ssocition between BP nd the sodium-to-potssium rtio, which is lso n index of dietry sodium intke, but they could not show ny direct reltionship between BP nd dietry sodium. 18 The contrdictory findings of these studies re indictive of the complex reltionship between BP nd dietry sodium. In this popultion, the complexity of this reltionship could be compounded by the high prevlence of obesity, 19 s body mss index (BMI) hs been shown to hve direct ssocition with BP A possibility exists tht obesity msks the reltionship between BP nd dietry sodium intke in this popultion. The biggest contributor to the msking effect could be the high proportion of overweight or obese individuls, especilly women. Therefore, in this study, in order to investigte whether the reltionship between dietry slt intke (indexed by 24-hour urinry sodium excretion) nd blood pressure is msked by obesity, we strtified prticipnts ccording to BMI sttus. Methods Informed consent ws obtined from the prticipnts, nd the principles of the Declrtion of Helsinki were dhered to. The

2 2 CARDIOVASCULAR JOURNAL OF AFRICA Advnce Online Publiction, Februry 2018 AFRICA study ws pproved by the University of the Witwtersrnd Committee for Reserch in Humn Subjects (pprovl number: M ) nd forms prt of the South Africn Hypertension nd Diet Study (SAHDS), which is prt of the ongoing Africn Project on Genes in Hypertension. The study design hs been briefly described in other publictions. 24,25 We rndomly recruited South Africns of Africn ncestry from metropolitn re of Johnnesburg (Soweto). Of these prticipnts, 547 (346 women nd 201 men) were selected becuse they hd complete 24-hour mbultory BP (ABP) nd 24-hour urine smples. The minimum ge for the study prticipnts ws 18 yers, nd there ws no upper ge limit. A stndrdised questionnire ws dministered to ech prticipnt to obtin demogrphic dt, medicl history such s the presence of hypertension, nd use of mediction. Height nd weight mesurements were recorded with the prticipnts wering indoor clothes with no shoes. BMI ws clculted s weight in kilogrms divided by the squre of height in metres. Twenty-four-hour mbultory BP monitoring ws performed using oscillometric monitors (Spcelbs, model 90207). Stndrd cuffs with n infltble bldder suitble for the prticipnt s rm circumference were used. The monitors were progrmmed to mesure BP t 15-minute intervls from 06:00 to 22:00 nd then t 30-minute intervls from 22:00 to 06:00. Prticipnts kept diry crd for the durtion of the recordings to note the time of going to bed in the evening nd time of wking up in the morning. These times were used to determine the wke nd sleeping periods. Prticipnts lso recorded the time when they took mediction, smoked, drnk cffeine or lcohol, depending on which ws pplicble to ech prticipnt. On completion of the recordings, dt were trnsferred to computer for nlysis. Ambultory blood pressure dt were expressed s 24-hour verge systolic nd distolic BP. Timed urine smples were collected over 24-hour period. Ech prticipnt ws issued with urine collection bottle nd the bottles were then collected from ech prticipnt fter 24 hours. Twenty-four-hour urine N + excretion rte ws clculted from the product of urine volume nd urine electrolyte concentrtion. Cretinine clernce ws determined from the product of urine volume nd urine cretinine concentrtions divided by plsm cretinine concentrtion. The qulity of urine smples ws determined by constructing regression reltions between 24-hour urine cretinine nd body weight, nd 24-hour urine volume nd ge in gender-specific groups. Bsed upon the 95% confidence intervls for ech group, 24-hour urine smple ws considered cceptble if 24-hour urine cretinine (mmol) ws > 3.5 nd < 35 for mles nd > 3.5 nd < 30 for femles. Smples with urine volumes < 500 ml/dy were lso ssumed to be incomplete urine collections. These re stndrd pproches nd hve been published on numerous occsions by other groups. Sttisticl nlysis For sttisticl nlysis the SAS softwre, version 9.4 (SAS Institute Inc, Cry, NC), ws used. Dt re shown s men ± SD nd p < 0.05 ws considered significnt. To determine the independent reltionship between 24-hour urinry excretion nd 24-hour systolic nd distolic BP, multivrite regression nlysis ws used. Confounders such s ge, gender, BMI (s continuous vrible), lcohol consumption, smoking, the presence of dibetes nd tretment of hypertension were included in the regression model. Results Tble 1 gives description of the demogrphic, nthropometric, hemodynmic nd generl clinicl chrcteristics of the prticipnts in this study. They were divided into three groups: totl smple, men nd women. The chrcteristics include ge, BMI, 24-hour mbultory BP, 24-hour urinry N + excretion rtes, lcohol consumption, smoking, dibetes sttus nd hormone concentrtions. The men ge of the totl popultion smple ws 45.3 ± 18.5 yers. There ws no ge difference between mles nd femles (men 45.5 ± 19.9 nd women 45.1 ± 17.7 yers) with 63.2% of prticipnts being women. The men BMI of the group ws 29.1 ± 7.8 nd 71% of prticipnts were either overweight or obese. When BMI ws clculted ccording to gender, more women were in the overweight/obese ctegory (75%) compred to men (47%). Thirty-five per cent (35%) of the totl smple popultion ws hypertensive, 23.0% consumed lcohol regulrly, 15% smoked, nd 14% hd dibetes mellitus or n HbA 1c > 6.1%. Tble 1. Generl nd clinicl chrcteristics of the study popultion ccording to gender nd BMI sttus Totl smple Men Women Prmeters All Norml Overweight b / Obese c All Norml Overweight/ Obese All Norml Overweight/ Obese Age (yers) 45.3 ± ± ± ± ± ± ± ± ± 16.1 BMI (kg/m 2 ) 29.1 ± ± ± ± ± ± ± ± ± 6.7 Hypertensive (%) Dibetic (%) Alcohol intke (%) Smokers (%) N + (mmol/dy) ± ± ± ± ± ± ± ± ±68.6* HbA 1c (%) 6.2 ± ± ± ± ± ± ± ± ± 1.5 Renin (ng/dl) 36.4 ± ± ± ± ± ± ± ± ± 5.0 Insulin (mmol/l) 14.4 ± ± ± 18.9* 13.8 ± ± ± 23.1* 14.8 ± ± ± 15.0 Leptin (ng/ml) 24.2 ± ± ± 29.4* 8.5 ± ± ± 8.4* 35.0 ± ± ± 28.1* HbA 1c, glycted hemoglobin; BMI, body mss index; N +, 24-hour urinry sodium excretion rte. Norml BMI is defined s < 25 kg/m 2, b overweight is defined s BMI 25 < 30 kg/m 2 nd c obese is defined s BMI 30 kg/m 2.

3 AFRICA CARDIOVASCULAR JOURNAL OF AFRICA Advnce Online Publiction, Februry Tble 2. Hemodynmic chrcteristics of the study popultion ccording to BMI sttus All prticipnts Norml BMI Overweight b /Obese c Totl smple SBP24 (mmhg) ± ± ± 16.1* DBP24 (mmhg) 72.2 ± ± ± 10.6* Women SBP24 (mmhg) ± ± ± 15.1* DBP24 (mmhg) 71.9 ± ± ± 9.9* Men SBP24 (mmhg) ± ± ± 15.7* DBP24 (mmhg) 64.4 ± ± ± 12.6* BMI, body mss index; SBP24, 24-hour mbultory systolic blood pressure; DBP24, 24-hour mbultory distolic blood pressure. Norml weight is defined s < 25 kg/m 2, b overweight is defined s BMI 25 < 30 kg/m 2 nd c obese is defined s BMI 30 kg/m 2. *p < 0.05 vs norml BMI. There ws no significnt difference in urinry sodium excretion in the totl smple nd in men; however the overweight/ obese women hd significntly lower urinry sodium excretion rtes. Both insulin nd leptin levels were significntly higher in the overweight/obese individuls compred to the normlweight prticipnts. Gender differences were observed in leptin concentrtions. Compred to men, leptin concentrtions were significntly higher in women. Tble 2 gives the hemodynmic chrcteristics of the popultion. Both systolic nd distolic BP vlues were higher in the overweight/obese prticipnts compred to the norml-weight prticipnts. Tble 3 shows the reltionship between 24-hour urinry sodium excretion nd 24-hour systolic nd distolic BP. There ws no significnt reltionship between 24-hour sodium excretion rte nd BP in the totl smple but when prticipnts were strtified ccording to BMI sttus, the reltionship reched sttisticl significnce in the norml-weight individuls, even though it remined insignificnt in the overweight/obese prticipnts. When prticipnts were divided ccording to gender, there ws significnt ssocition between urinry sodium excretion rte nd BP in the totl smple of men nd in the normlweight men but not in overweight men. In women there ws no reltionship between 24-hour urine excretion nd BP, irrespective of BMI sttus. Fig. 1 compres the slopes of the reltionship between 24-hour urinry sodium excretion nd BP in the totl popultion. The slope (β-coefficient) of the norml-bmi prticipnts ws significntly higher thn tht of the overweight/ obese group. Discussion To determine the msking effects of n incresed BMI, we first investigted the reltionship between 24-hour urinry sodium excretion nd BP in the totl popultion smple. Consistent with previous studies in this popultion 4-6 nd in other popultion groups, 29,30 we found no reltionship. In spite of the inconclusive results in this popultion, the reltionship between sodium level nd BP hs been well estblished in number of studies, therefore our current findings require thorough scrutiny. The limittions of previous studies conducted in this popultion could be tht they did not tke into considertion the high prevlence of obesity. So in order to ccount for the high incidence of obesity, in this study we strtified prticipnts ccording to BMI sttus. In multivrite regression nlysis, there ws sttisticlly significnt reltionship between 24-hour urinry sodium excretion nd both systolic nd distolic BP. However sodium level ws not relted to BP in the overweight/obese group. This difference ws further demonstrted when the slopes of this reltionship were compred between the two groups. The β-coefficients of the norml-bmi prticipnts were significntly higher thn those of the overweight/obese groups. This is indictive of stronger reltionship in the norml-weight group compred to the overweight/obese individuls. β-coefficient of urinry N + (mmol/dy) vs BP (mmhg) SBP24 * DBPD Totl popultion Norml BMI Overweight/obese Fig. 1. Multi-djusted slopes (β-coefficients) of 24-hour urinry sodium excretion versus 24-hour systolic nd distolic blood pressure in the totl smple, norml-weight nd overweight/obese prticipnts. Adjustments were mde for ge, gender, smoking, lcohol intke, dibetes nd hypertension. BMI, body mss index; BP, blood pressure; SBP24, 24-hour systolic blood pressure; DBP24, 24-hour systolic blood pressure. * Tble 3. Reltionship between dietry sodium intke nd 24-hour mbultory BP ccording to gender nd BMI sttus Totl smple Men Women All prticipnts Prtil r 2 95% CI p-vlue Prtil r 2 95% CI p-vlue Prtil r 2 95% CI p-vlue SBP24 (mmhg) * DBP24 (mmhg) * Norml BMI SBP24 (mmhg) * * DBP24 (mmhg) * * Overweight b /obese c SBP24 (mmhg) DBP24 (mmhg) CI, confidence intervls; SBP24, 24-hour systolic blood pressure; DBP24, 24-hour distolic blood pressure; BMI, body mss index. Norml BMI is defined s < 25 kg/m 2, b overweight is defined s BMI 25 < 30 kg/m 2 nd c obese is defined s BMI 30 kg/m 2. Adjustments were mde for ge, gender (in the totl popultion), BMI (s continuous vrible), hypertension, dibetes, smoking nd lcohol intke.

4 4 CARDIOVASCULAR JOURNAL OF AFRICA Advnce Online Publiction, Februry 2018 AFRICA The differences in the reltionship between the two groups re indictive of the msking effects of obesity. These msking effects were further confirmed when the prticipnts were divided ccording to gender. In men, the reltionship ws present in the totl smple of men nd in the len group but not in the overweight/obese group. In the women, no reltionship ws observed irrespective of BMI sttus. The gender differences re due to dissimilrities in the degree of obesity in the two groups. In men the verge BMI ws 24.9 ± 5.0 kg/m 2 nd only 47% were overweight or obese. On the other hnd the verge BMI in women ws 31.5 ± 8.1 kg/m 2 with 75% of the women in the overweight/obese ctegory. Due to the lower BMI nd lower proportion of overweight/obese men, the reltionship between sodium nd BP ws not msked. On the other hnd, the significntly higher BMI nd higher proportion of overweight/obese women resulted in the msking of the reltionship in the femle group. Since women mde up 63% of the totl popultion smple, the msking effects of this femle group re imputed to the whole popultion smple. Mechnisms responsible for the msking effects seem to be medited by leptin. Plsm renin nd insulin levels were similr between the different groups but leptin ws significntly higher in the overweight/obese group, especilly in women. This could ccount for the significntly lower urinry sodium excretion rte in the overweight/obese women compred to norml-weight women. As explined erlier, women mde up 63% of this popultion nd 75% of them were overweight or obese, therefore they were responsible for the significntly lower urinry sodium excretion rte (106 mmol/dy) in this popultion compred to other popultion groups. In study conducted in 45 countries with totl of prticipnts, the verge 24-hour urinry sodium excretion rte ws mmol/dy. 35 In Chinese study, the verge 24-hour urinry sodium excretion ws 235 mmol/dy, 3 which is more thn double tht of our popultion. A low sodium excretion rte of 104 mmol/dy ws observed in the trils of the Hypertension Prevention Collbortive Reserch Group. 36 However in this study, the prticipnts were on low-sodium diet. The reltively low urinry sodium excretion rte is unique to our popultion smple nd it my ccount for the leptin-medited msking effects. The significntly higher leptin concentrtions in the overweight/obese groups, especilly in women where it ws more thn three times higher thn tht of the overweight/obese mles, medited the msking effects. Normlly sodium intke results in slight increse in BP due to volume expnsion. This cuses n incresed sodium excretion rte through pressure ntriuresis. A stedy stte is reched where sodium intke is equl to sodium excretion. However in the presence of high leptin concentrtions the stedy stte is not chieved. Although leptin stimultes the sympthetic nervous system, it lso increses nitric oxide concentrtion. 37 Therefore, the pressor effects of the sympthetic nervous system re countercted by the depressor effects of nitric oxide. Consequently there is no net chnge in BP. Without n increse in BP, pressure ntriuresis is suppressed, resulting in reduced urinry sodium excretion rte. This explins the significntly lower urinry sodium excretion rtes in overweight/obese women nd in the totl popultion smple since women constituted 63% of this smple. The low urinry sodium concentrtion leds to nrrow rnge of urinry sodium concentrtion. As consequence, the reltionship between 24-hour urinry sodium excretion nd BP is blunted. The msking of reltionship due to low concentrtions is clled regression dilution. 3 To the best of our knowledge, this is the first study to show tht incresed BMI msks the reltionship between 24-hour urinry sodium excretion nd BP, nd tht leptin medites the mechnisms responsible for the msking effect. Potentil limittions of our study re s follows; firstly, we collected once-off 24-hour urine smples nd this does not ccount for the dily vrition in dietry sodium intke. Although 24-hour urinry sodium excretion is n cceptble index of dietry sodium intke, the once-off 24-hour urine smple does not tke into ccount the within- nd betweenperson sodium intke vritions. Secondly, the covrites such s lcohol intke nd smoking were obtined through self-reported questionnire nd therefore my not hve been ccurte. Thirdly, we did not use dietry recll questionnire to ssess sodium intke. This could hve been useful tool for ssessing the ccurcy of 24-hour urinry sodium excretion s n index of dietry sodium intke. Finlly, this ws cross-sectionl study, therefore conclusions regrding cuse nd effect must be drwn with cution. Conclusion This study indictes tht dietry sodium intke influenced BP in this popultion, however this reltionship could only be observed in len prticipnts, since incresed BMI msked this reltionship. These dt suggest tht future studies must tke into ccount the high prevlence of obesity in this popultion before ny conclusions re drwn on the reltionship between sodium intke nd BP. References 1. Sttistics South Afric (STATSSA). Mortlity nd cuses of deth in South Afric, 2013: Findings from deth notifictions. Sttisticl Relese. (P0309.3). Pretori: Government Printers, Mensh GA, Roth GA, Smpson UKA, Morn AE, Feigin VL, Forouznfr MH, et l. For the GBD 2013 mortlity nd cuses of deth collbortors. Crdiovsc J Afr 2013; 26(2): S6 S Yn L, Bi Z, Tng J, Wng L, Yng Q. 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