The association between obesity and cardiac output (CO)

Transcription

1 Relations of Stoke Volume and Cadiac Output to Body Composition The Stong Heat Study Taquin Collis, MD; Richad B. Deveeux, MD; May J. Roman, MD; Giovanni de Simone, MD; Jeun-Liang Yeh, PhD; Babaa V. Howad, PhD; Richad R. Fabsitz, MA; Thomas K. Welty, MD Backgound Although cadiac output (CO) plays the vital ole of deliveing nutients to body tissues, few data ae available concening the elations of stoke volume (SV) and CO to body composition in lage population samples. Methods and Results Dopple and 2D echocadiogaphy and bioelectic impedance in 2744 Stong Heat Study paticipants wee used to calculate SV and CO and to elate them to fat-fee body mass (FFM), adipose mass, and demogaphic vaiables. Both SV and CO wee highe in men than women and in oveweight than nomal-weight individuals, but these diffeences wee diminished o even evesed by nomalization fo FFM o body suface aea. In both sexes, SV and CO wee moe stongly elated to FFM than adipose mass, othe body habitus measues, ateial pessue, diabetes, o age. In multivaiate analyses using the aveage of Dopple and left venticula SV to minimize measuement vaiability, FFM was the stongest coelate of SV and CO; othe independent coelates wee adipose mass, systolic pessue, diabetes, age, and use of digoxin and calcium channel and -blockes. Conclusions In a population-based sample, SV and CO ae moe stongly elated to FFM than othe vaiables; inceased FFM may be the pimay deteminant of inceased SV and CO in obesity. (Ciculation. 2001;103: ) Key Wods: Ameican Indians diabetes mellitus echocadiogaphy venticles The association between obesity and cadiac output (CO) has been obseved since the 1950s, when Alexande et al 1 chaacteized obesity as a state in which elevated blood volume, enlaged vascula tee, and inceased CO wee all thought necessay to sustain the metabolic demands of an expanded adipose tissue mass. Messeli et al 2 late confimed inceases in intavascula volume in obese subjects and demonstated that this elevation of CO was elated pimaily to inceases in stoke volume (SV) athe than in heat ate. The obseved changes in total blood volume and CO wee again assumed to be seconday to metabolic demands of excess adipose tissue. 2,3 Oveweight, howeve, is also associated with inceased fatfee mass (FFM), 4 and the elative contibutions of adipose body mass and FFM as deteminants of CO have not been studied to date. Because FFM epesents metabolically active tissue and because the inceased weight in obese individuals is in pat due to inceased FFM, the pesent study was undetaken to test the hypothesis that FFM is a stonge deteminant of SV and CO than adipose mass o othe clinical chaacteistics. An additional goal was to detemine whethe diffeences in FFM between oveweight and nomal-weight adults might account fo the inceased CO in the fome goup. Methods The Stong Heat Study (SHS) is a population-based suvey of cadiovascula isk factos and pevalent and incident cadiovascula disease in Ameican Indian communities in Aizona, Oklahoma, and South and Noth Dakota. As peviously descibed, 5 7 membes of 3 tibal communities in Aizona, 7 in Oklahoma, and 3 in South/Noth Dakota, 45 to 74 yeas old, wee ecuited fom tibal membes living on esevations o (in Oklahoma) in a defined geogaphic aea (oveall paticipation ate 62%) fo an initial examination in 1989 to The second SHS examination was conducted in 1993 to 1995 to assess change in body habitus, blood pessue, and othe baseline measues and to add echocadiogaphy among suviving paticipants. 7 Standadized measuements of seated bachial blood pessue; anthopometic measues, including height, weight, body mass index (BMI), waist/hip atio, and pecent body fat by bioelectic impedance; fasting glucose, insulin, lipid, and lipopotein concentations; and 2-hou glucose toleance test and glycosylated hemoglobin levels wee obtained. Diabetes was diagnosed by Wold Health Oganization citeia. 8 FFM and adipose body mass wee estimated by use of an RJL impedance mete 5 (model B1410) and equations based on total body wate: Wate males (L) e { log [height (cm)] log [esistance ( )] log [weight (kg)]}. Wate females (L) e { log [height (cm)] log [esistance ( )] log [weight (kg)]}. Received June 1, 2000; evision eceived Septembe 27, 2000; accepted Octobe 4, Fom Conell Medical Cente, New Yok, NY (T.C., R.B.D., M.J.R., G.d.S.); Univesity of Oklahoma Health Sciences Cente, Oklahoma City (J.-L.Y.); MedSta Reseach Institute, Washington, DC (B.V.H.); National Heat, Lung, and Blood Institute, Bethesda, Md (R.R.F.); and Abedeen Aea Tibal Chaimen s Health Boad, Rapid City, SD (T.K.W.). The views expessed in this aticle ae those of the authos and do not necessaily eflect those of the Indian Health Sevice. Coespondence to Richad B. Deveeux, MD, Division of Cadiology, Box 222, Conell Medical Cente, 525 E 68th St, New Yok, NY bdevee@med.conell.edu 2001 Ameican Heat Association, Inc. Ciculation is available at 820

2 Collis et al Fat-Fee Mass, Adipose Mass, and Cadiac Output 821 TABLE 1. Subject Chaacteistics Nomal Weight (n 1249) P, Weight Sex Men (n 951) Women (n 1793) P, Sex Oveweight (n 1490) P, Weight Age, y NS Height, cm NS Weight, kg NS BSA, m NS BMI, kg/m FFM, kg Adipose mass, kg % Adipose mass Waist/hip atio Dopple SV, ml NS Aveage SV, ml NS Dopple CO, L/min NS Aveage CO, L/min NS BSA indicates body suface aea. FFM wate (L)/ Adipose body mass weight FFM. Assessment of FFM by bioelectic impedance has been validated in Ameican Indians by compaison with FFM detemined by undewate weighing alone o in combination with dual-enegy x-ay absoptiomety ( 0.86 to 0.97). 9,10 To calculate waist/hip atio, waist cicumfeence was measued in the supine position with an anthopometic tape; hip cicumfeence was measued at the maximum potusion of the gluteal muscles in the standing position. Oveweight was ecognized by BMI 27.3 kg/m 2 in men and 27.8 kg/m 2 in women. Fo the pesent study, paticipants wee included if they had technically satisfactoy Dopple echocadiogaphic measuements of SV, CO, and bioelectic impedance measuements and no hemodynamically significant ( 2 ) aotic o mital egugitation by colo Dopple echocadiogaphy. Echocadiogaphic Methods Studies wee pefomed by a potocol peviously descibed in detail 11,12 using phased-aay echocadiogaphs with M-mode, 2D, and pulsed and colo-flow Dopple capabilities. Subjects wee examined with the head of the examining table elevated 30 in the patial decubitus position. Pulsed Dopple sample volumes wee placed at the cente of the aotic annulus in the apical long-axis o five-chambe view to ecod systolic tansaotic blood flow. Echocadiogaphic Measuements Coect oientation of planes fo imaging and Dopple ecodings was veified as peviously descibed. 13 Measuements wee made with computeized eview stations equipped with digitizing tablet and monito sceen ovelay fo calibation and measuement. Left venticula (LV) intenal dimension and septal and posteio wall thicknesses wee measued at end diastole and end systole by Ameican Society of Echocadiogaphy (ASE) M-mode ecommendations 14 on up to 3 cadiac cycles. When optimal oientation of the LV cuso could not be obtained, coectly oiented linea dimension measuements wee made by the ASE 2D leading-edge convention. 15 The diamete of the aotic annulus was measued in the long-axis view that maximized it fom tailing edge to leading edge at the hinging points of the aotic cusps to the annulus, with colo Dopple used to claify tissue-blood intefaces if necessay. 16 Dopple tansaotic flow was assessed in the pojection in which peak flow velocity was maximal by tacing the black-white inteface outlining the Dopple flow envelope, as peviously shown to yield accuate estimates of invasively measued SV. 17 Heat ate was measued simultaneously. Dopple colo-flow maps and, when applicable, pulsed-wave ecodings wee used to gade mital and aotic egugitation on a scale of 0 to 4 by standad citeia. 18,19 Calculation of Deived s Dopple SV was calculated as aotic annula coss-sectional aea (in squae centimetes) times the aotic time-velocity integal in centimetes. CO was deived as SV times heat ate. SV was also measued fom LV end-diastolic and end-systolic volumes calculated fom LV intenal dimensions by a method validated in individuals with nomal-sized to dilated LVs. 20 To assess whethe educing the vaiability of SV and CO by aveaging esults of 2 measuements would stengthen thei elations to body habitus and othe vaiables, aveage SV and CO wee calculated as the mean of Dopple and LV measuements. Data Handling and Statistical Analyses Data ae pesented as mean SD fo continuous vaiables and popotions fo categoical vaiables. Because of the known impact of sex on body composition, analyses wee pefomed sepaately in men and women. Patial coelations between independent vaiables and SV and CO wee adjusted fo possible cente effects by use of 2 dummy vaiables. Multiple linea egession analysis using an ente pocedue with assessment of collineaity diagnostics was used to detemine the independence of coelates of SV and CO. Measues of body composition consideed in these analyses wee FFM and adipose mass, height to the powe of its allometic elations with SV and CO (height 2.04 and height 1.83, espectively 21 ), BMI, and waist/hip atio. Patial coelation coefficients wee used to estimate the popotion of vaiance of dependent vaiables explained by each independent vaiable. The stength of coelations of diffeent vaiables to the same efeence standad was compaed by use of Fishe s z statistic. Two-tailed P 0.05 indicated statistical significance. Results Technically satisfactoy Dopple echocadiogams, body composition measuements, and othe needed clinical data fo the pesent study wee obtained in 2744 paticipants in the second SHS examination without 2 aotic o mital egugitation o segmental LV wall motion abnomalities (Table 1). Ages of men and women anged fom 48 to 81 and

3 822 Ciculation Febuay 13, 2001 TABLE 2. Univaiate Coelates of Stoke Volume in Men and Women Men (n 928) Women (n 1764) (Dopple) (aveage) P (Dopple) (aveage) FFM Adipose mass 0.22* 0.26* Waist/hip atio 0.18* 0.21* * 0.11* BMI 0.24* 0.28* Body weight Systolic pessue 0.08* 0.09* NS/ * 0.12* Height 0.14* 0.18* * 0.19* Height * 0.18* * 0.19* Age 0.06* 0.08* NS/ * 0.04* NS/NS *P 0.05 vs sex-specific coelations between SV and FFM using Fishe s z statistic. P 46 to 80 yeas, espectively. All measues of body size, including FFM, wee highe in men, wheeas body adiposity was geate in women. SV and CO wee highe by 10% in men; mean diffeences wee simila fo aveage SV and CO, with smalle SDs. Oveweight individuals wee younge, heavie, and had highe adipose mass, pecent body fat, and waist/hip atio than nomal-weight paticipants. FFM was highe, by a mean of 14%, and SV and CO wee 9% highe in oveweight individuals. Use of aveage values of SV and CO esulted in nealy identical mean diffeences between goups with smalle SDs. TABLE 3. Univaiate Coelates of Cadiac Output in Men and Women Men (n 925) (Dopple) (aveage) P (Dopple) Coelates of SV In men, SV coelated bette with FFM than with adipose mass, BMI, waist/hip atio, height, o height 2.04 (Table 2). SV had a weak positive elation with systolic pessue and a weak negative one with age. Body weight was as stong a coelate of SV as FFM. Aveage SV had a simila patten of elationships, with geneally slightly highe coelation coefficients. In women, SV was modeately and equivalently coelated with FFM, adipose mass, body weight, and BMI. Weake, but still significant, positive elations wee obseved between SV and waist/hip atio, height and height 2.04, and systolic pessue but not age. Aveage SV had a minimally stonge set of elations with body habitus vaiables and SV. SV (as well as CO) was highe (P 0.001) in diabetic women. Coelates of CO In men, CO was moe closely coelated with FFM than adipose mass, waist/hip atio, height, o height 1.83 (Table 3). Relations of CO with body weight and BMI, howeve, wee simila to that with FFM. CO also had a weak positive elation with systolic pessue and a weak negative one with age. Aveage CO was coelated slightly moe closely with most measues of body size and systolic pessue. CO was highe in diabetic than nondiabetic men (mean, 5.3 vesus 5.0 L/min, P 0.001) because of highe heat ate. Among women, CO had simila modeate, positive elations with FFM and body weight and slightly weake ones with adipose mass and BMI. Positive, but moe weakly positive, elations wee obseved between CO and waist/hip atio, height, height 1.83, and systolic pessue but not age. Use of aveage CO slightly stengthened most elations, except those with height. Women(n 1757) (aveage) FFM Adipose mass Waist/hip atio 0.23* 0.24* * 0.15* Body mass index Weight Systolic pessue * * 0.11* Height 0.12* 0.16* * 0.17* Height * 0.16* * 0.17* Age 0.14* 0.18* * 0.08* /0.001 *P 0.05 vs sex-specific coelation between CO and FFM using Fishe s z statistic. P

4 Collis et al Fat-Fee Mass, Adipose Mass, and Cadiac Output 823 TABLE 4. Multivaiate Coelates of Stoke Volume in Men and Women Men (R 0.31) (n 925) Women (R 0.41) (n 1757) B SEM P B SEM P FFM Adipose mass Diabetes Systolic blood pessue NS Age NS Constant Multivaiate Analyses SV had the stongest independent positive coelation with FFM, followed by adipose mass, in both sexes (Table 4). Diabetes had an independent negative elation with SV in men, with a paallel tend in women; systolic pessue had a weak positive elation to SV in women, with a paallel tend in men; age did not ente the model in eithe sex. When women and men wee consideed togethe, with an indicato vaiable fo sex, lage SV was independently elated to highe FFM ( 0.333), adipose mass ( 0.181), absence of diabetes ( 0.081), and highe systolic pessue ( 0.061, all P 0.001) but not age o sex. Altenative analyses used aveage SV as the dependent vaiable. In men, the multiple R inceased fom 0.31 to 0.39 because of stonge associations with FFM ( 0.286), adipose mass ( 0.148), and absence of diabetes ( 0.138) (all P 0.001) but not age o systolic pessue. In women, the multiple R also inceased (0.44 vesus 0.41), pincipally because of stonge association with FFM ( 0.285), with smalle inceases in associations with adipose mass ( 0.198), systolic pessue ( 0.092), and absence of diabetes ( 0.073) but not age. When women and men wee consideed togethe, the multiple R inceased slightly (fom 0.39 and 0.44 in the 2 sexes to 0.48), with aveage SV most stongly associated with highe FFM ( 0.416), followed by highe adipose mass ( 0.181) and systolic pessue ( 0.083) and absence of diabetes ( 0.107) (all P 0.001). In futhe analysis consideing majo cadioactive medications, SV was independently elated (R 0.51) to FFM ( 0.419), adipose mass ( 0.219), absence of diabetes ( 0.094), highe systolic pessue ( 0.087) (all P 0.001), and use of digoxin ( 0.061, P 0.002) and calcium blockes ( 0.060, P 0.003) but not sex, age, o use of diuetics, ACE inhibitos, o -blockes. Sex-specific egession analyses to identify independent coelates of CO ae summaized in Table 5. In both sexes, FFM was the stongest coelate of CO. Adipose mass was the second stongest coelate of CO in women but was not independently associated with it among men. In both sexes, systolic pessue was positively associated with CO, wheeas age and diabetes wee not. When the sexes wee combined, CO was most stongly (R 0.39) associated with FFM ( 0.304), followed by adipose mass ( 0.159) and systolic pessue ( 0.092, all P 0.001) but not age, diabetes, o sex. Altenative egession analyses used aveage CO as the dependent vaiable. The multiple R inceased slightly in women (R 0.42 vesus 0.39), pincipally because of the stonge association with FFM ( 0.292, P 0.001), with minimal changes in associations with adipose mass ( 0.137, P 0.001) and systolic pessue ( 0.087). In men, multiple R inceased modestly (0.39 vesus 0.34) because of stonge positive associations of CO with FFM ( 0.257) and systolic pessue ( 0.124, both P 0.001) and stonge negative association with age ( 0.098, P 0.004), with unchanged positive association with adipose mass ( 0.096, P 0.021). When the sexes wee combined, CO had positive elations to FFM ( 0.372), adipose mass ( 0.145), and systolic pessue ( 0.105; all P ) and a negative one with age ( 0.054, P 0.004) but not diabetes o sex (R 0.43). In futhe analysis that also consideed cadioactive medications, CO was independently elated (R 0.46) to FFM ( 0.368), adipose mass ( 0.171), systolic pessue ( 0.102) (all P 0.001), calcium blocke use ( 0.072) and absence of -blocke use ( 0.071) (both P 0.001), younge age ( 0.050, P 0.024), and digoxin use ( 0.044) but not sex, diabetes, o diuetic o ACE inhibito use. Associations of Sex and Obesity With Diffeent Nomalizations of SV and CO Absolute SV and CO wee highe in men than women, wheeas nomalization fo body suface aea eliminated the sex diffeence in SV and esulted in maginally highe cadiac index in women (Table 6). SV and CO nomalized fo FFM wee consideably smalle in men than women. Aveage SV and CO had vitually identical mean sex diffeences, with smalle within-goup SDs. Oveweight paticipants had highe absolute SV and CO than nonoveweight paticipants, wheeas these diffeences wee eliminated by nomalization fo body suface aea and evesed by indexation by FFM. These findings wee confimed in analyses using aveaged Dopple and LV deteminations of SV and CO. Discussion To the best of ou knowledge, this is the fist study to examine the elations of SV and CO to FFM and adipose mass in a lage population sample. The pincipal finding of the study is that both SV and CO ae moe stongly elated to FFM than to adipose mass, othe anthopometic measues,

5 824 Ciculation Febuay 13, 2001 TABLE 5. Multivaiate Coelates of Cadiac Output in Men and Women Men (n 925) (R 0.34) Women (n 1757) (R 0.39) B SE P B SE P FFM Adipose mass Diabetes NS Systolic blood pessue Age NS Constant sex, age, blood pessue, diabetes, o effects of cadioactive medications. These esults, although new, ae not supising in view of studies demonstating inceased FFM in obese individuals in a vaiety of populations and age goups: FFM accounts fo 20% to 40% (aveage, 29%) of the weight diffeence between lean and oveweight goups. 4 Consistent with these obsevations, FFM accounted fo 6.8 kg, o 30%, of the 22.5 kg geate body weight in oveweight than nomal-weight SHS paticipants. Results of Multivaiate Analyses When both sexes wee combined, with addition of an indicato vaiable fo sex, Dopple SV was most stongly elated to FFM, with associations, as judged by standadized egession coefficients ( ), 67% as stong with adipose body mass and 25% as stong with systolic pessue and absence of diabetes. Neithe sex no age was independently associated with Dopple SV in this model. In a simila analysis, CO was most stongly elated to FFM, with additional associations 50% as stong with adipose mass and 25% as stong with systolic blood pessue and absence of diabetes but not sex o age. These obsevations ae in accod with pevious evidence that diffeent nomal limits fo indexed SV o CO ae not needed in elation to eithe sex o age among adults. 21 Impact of Using Aveage of Dopple and LV Measuements One poblem in assessing the deteminants of many physiological measuements, exemplified by ateial pessue, is consideable between-measuement vaiability. Although use of many measuements is optimal, 22 up to a 30% eduction in TABLE 6. vaiability can be obtained by using one additional measuement. In the pesent study, we took advantage of the fact that ou potocol povides sepaate measuements of SV by validated Dopple and LV methods 11,17 to calculate aveage SV and, consequently, aveage CO. As expected, aveage SV and CO showed lowe within-goup vaiability and had somewhat stonge elations than pimay Dopple measuements with body habitus vaiables. Of geatest biological impotance, use of aveaged measues of cadiac pump function inceased the dispaity between FFM and adipose mass as independent deteminants theeof. Additional consideation of medication usage confimed these esults and evealed independent associations between digoxin o calcium blockes and SV (with mean incements of 5.9 and 2.2 ml) and between digitalis, calcium blockes, and -blockes and cadiac index (by 357, 234, and 356 ml min 1 m 2 on aveage). Physiological Mechanisms FFM (compising ogan cell mass and nonfatty tissues, including tendons, ligaments, and bone) 23 epesents metabolically active tissue; up to 99% of body metabolism takes place in the body cell mass. 24 Given that CO is known to be intimately elated to the level of metabolism, though tissue demands fo oxygen, 25 it is tempting to ascibe the impotance of FFM as a coelate of CO in both lean and obese subjects to the metabolic load accompanying FFM and to attibute pat of the inceased CO of obesity to inceased FFM associated with obesity. In addition to associations between FFM and SV and CO, the pesent study has also shown the latte vaiables to be moe weakly associated with adipose mass. These associations may eflect blood flow needed to suppot the enegy Effect of Sex and Oveweight on Diffeent Indexations of Stoke Volume and Cadiac Output Men (n 925) Women (n 1757) P Nomal Weight (n 1222) Oveweight (n 1465) P P, Inteaction SV, ml SV/Body suface aea, ml/m NS NS NS SV/FFM, ml/kg SV/height CO, ml/min NS CO/body suface aea, ml min 1 m NS NS NS CO/FFM, ml kg 1 min CO/height

6 Collis et al Fat-Fee Mass, Adipose Mass, and Cadiac Output 825 expenditue, albeit small, of adipose tissue as well as possible shunt flow though this tissue and inceased cutaneous blood flow to dissipate body heat in oveweight individuals. In addition, despite easonable accuacy of bioelectic impedance FFM measuements, esidual eos may have attibuted some FFM to adipose mass, theeby oveestimating the associations of adipose mass with CO. One impotant esult of the pesent study is that only a small potion of vaiability of SV and CO is associated with and thus potentially explained by body composition and demogaphic chaacteistics that wee consideed, with R 2 values anging fom 0.10 to 0.26 in multivaiate analyses. Because the facto associated with esting CO that is most stongly physiologically egulated is matching oxygen delivey to tissue needs, the CO needed fo a given level of tissue metabolism will be invesely elated to blood hemoglobin concentation. It is attactive to speculate that highe SV and CO indexed fo FFM in women than men may have been a compensation fo lowe hemoglobin concentation in women. 26 Unfotunately, hemoglobin was not measued in the pesent study. Acknowledgments This study was suppoted in pat by gants U01-HL-41642, U01- HL-41652, and U01-HL fom the National Heat, Lung, and Blood Institute and M10-RR (GCRC) fom the National Institutes of Health, Bethesda, Md. We would like to thank Indian Health Sevice facilities, SHS paticipants, and paticipating tibal communities fo the extaodinay coopeation and involvement that made this study possible; Betty Javis, RN, Tauqee Ali, MD, and Alan Cawfod fo study cente coodination; Tauqee Ali, MD, Helen Beaty, Joan Cate, Michael Cyl, and Neil Sikes fo expet pefomance of echocadiogams; and Viginia Buns fo invaluable assistance in manuscipt pepaation. Refeences 1. Alexande SK, Dennis EW, Smith WG, et al. 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