Bdy Weight, Cerebral Athersclersis and Cerebral Vascular Disease: An Autpsy Study BY A. C. KLASSEN, M.D., R. B. LOEWENSON, Ph.D., AND J. A. RESCH, M.D. Abstract: Bdy Weight, Cerebral A thersclersis and Cerebral Vascular Disease: An Autpsy Study The severity f athersclertic invlvement f intracranial cerebral arteries was assessed at autpsy in 3,3 adult subjects. Pnderal index values were calculated fr each sex and ten-year age grup. In mst age grups, subjects with cerebral vascular disease, r ne r mre f several cnditins knwn t be assciated with increased cerebral athersclersis, had higher relative bdy weight than did subjects withut thse cnditins. Subjects in the lwer quartile f pnderal index distributin ("verweight" grup) had mre severe cerebral athersclersis than did subjects in the upper quartile ("underweight" grup). Hwever, when subjects with disease cnditins knwn t be assciated with increased cerebral athersclersis were excluded frm the analysis, n relatinship between relative bdy weight and severity f cerebral athersclersis culd be demnstrated. Clinical and/r pathlgical evidence f cerebral vascular disease was apparently present mre ften in "verweight" than in "underweight" subjects, at least in certain age grups. Additinal Key Wrds verweight strke underweight pnderal index Intrductin D Numerus studies, especially thse based n life insurance data, have demnstrated an assciatin between excessive bdy weight r besity and increased mrtality rates. 1 " 4 Excessive adipsity r relative besity als has been demnstrated t be assciated with hypertensin, 6 ' 6 impaired glucse tlerance, and elevated serum lipid values. Therefre, it might be expected that relative besity wuld be assciated, in turn, with increased mrtality and mrbidity due t ischemic cardiac disease and cerebral vascular disease. Such assciatins, especially between besity and cerebral vascular disease, as yet have nt been clearly established. 7 " 9 The present study examines the relatinship between terminal bdy weight and the degree r severity f cerebral athersclersis in an autpsy ppulatin. The pssibility f a relatinship between bdy weight and the prevalence f cerebral vascular disease in the same ppulatin als is explred. The study is based n the assumptin that athersclersis f cerebral arteries is prbably etilgically related t the subsequent develpment f clinical and/r pathlgical evidence f cerebral vascular disease. Frm the Department f Neurlgy, University f Minnesta Health Sciences Center, 4 Sutheast Unin Street, Minneaplis, Minnesta 55455. The facilities f Health Cmputer Sciences, University f Minnesta Health Sciences Center (NIH Grant RR-67), were used in this study. Supprted by NINDS Grant Number NS-3364. Methds The intracranial cerebral arteries utilized in this study were btained frm subjects underging cnsecutive rutine autpsies at the University f Minnesta Hspitals and Hennepin Cunty General Hspital (Minneaplis, Minnesta) during the years 1961 t 1965. The clinical and pathlgical data were btained by retrspective review f the hspital recrds and pathlgical reprts. Of a ttal f 3,94 subjects ver 19 years f age, infrmatin regarding bdy weight and height was available in 3,3 and, hence, nly the latter were included in this study. Bdy weight and height measurements were btained frm the hspital clinical recrd using the last recrded height and weight during the terminal illness. When n "live" terminal measurements were available, the autpsy measurements were used. Table 1 lists the numbers f subjects by sex and ten-year age grups. The pnderal index, r the rati f height in inches t the cube rt f the weight in punds, was used as a measure f bdy weight relative t bdy height. A lw pnderal index value thus crrespnds t high relative bdy weight and a high pnderal index t a lw bdy weight. Fr each sex and ten-year age grup, the distributins f the pnderal index values were determined. The subjects in the lwest and highest quartiles f the pnderal index distributins were then designated as "verweight" and "underweight," respectively. The semiquantitative scring methd fr assessing the severity f athersclertic invlvement f cerebral arteries has been previusly described and validated. 1 - " In brief, the methd assigns a numerical grade f t 4 related t the degree f luminal encrachment by athersclersis t each f sites in the circle f Willis and its majr branches. The sum f the grades fr all sites is utilized as the numerical 31 Strke, Vl. 5, May-June 1974
BODY WEIGHT, CEREBRAL ATHEROSCLEROSIS AND CVD TABLE 1 Numbers f Subjects by Age and Sex Age grup Female* -9 3-39 4-49 5-59 6-69 7-79 8 + Ttal 137 5 75 454 439 41 5,5 7 13 45 74 8 13 76 1,9 cerebral athersclersis vessel scre fr each subject. Vessel scre distributins were btained fr each sex and in each ten-year age grup. Percentiles f pnderal index and vessel scre distributins were utilized fr purpses f this presentatin. The 5th and 75th percentiles f the pnderal index distributins determined the lwer and upper quartiles, that is, the "verweight" and "underweight" grups, respectively. Fr these tw grups the median vessel scres were pltted at the apprpriate midpints f the ten-year age intervals t prvide a graphical cmparisn f cerebral athersclertic invlvement between "verweight" and "underweight" subjects. Previus studies using this same autpsy ppulatin have demnstrated that certain clinical and pathlgical disease cnditins are assciated with increased severity f cerebral athersclersis. 1 These cnditins r disease states include cerebral vascular disease, athersclertic heart disease, diabetes mellitus, and hypertensin. Because these disease states als may be assciated with besity, further data analysis regarding pssible relatinships between relative bdy weight and cerebral athersclersis was perfrmed after exclusin f subjects with ne r mre f the abvementined cnditins. Table lists the sample sizes in each f the disease subgrups fr subjects fr whm clinical and pathlgical infrmatin as well as pnderal index values were available. Because f the high prevalence f these diseases, especially in the lder age grups, the sample sizes fr the remaining cases are quite small; age grups with sample sizes f less than ten subjects were mitted frm the analysis. Median values f pnderal index als were btained fr subjects with and withut clinical r pathlgical evidence f cerebral vascular disease. Similarly, median values f pnderal index fr subjects with ne r mre f cerebral vascular disease, athersclertic heart disease, diabetes TABLE Disease Subgrups Assciated With Increased Cerebral Athersclersis Cerebral vascular disease Athersclertic heart disease Diabetes mellitus Hypertensin One r mre f the abve Malef (n = 1,5) 334 1,31 114 3 Femalei (n = 1,9) 179 446 1 48 1,7 61 mellitus, and hypertensin were cmpared with thse f subjects withut these cnditins. Finally, the frequency f ccurrence f cerebral vascular disease was determined in subjects in the "verweight" and "underweight" grups using the clinical recrds and brain autpsy reprts. Results Pnderal index distributins, including the 5th, 5th (median), and 75th percentiles, fr ten-year age grups are pltted in figure 1. In males, pnderal index remained relatively cnstant in all age grups. In females, a gradual tendency tward lwer pnderal index, that is, increased relative weight, with increasing age was nted which cntinued until the eighth decade; in the ldest age grup the relative weight was decreased. Subjects in whm there was clinical r pathlgical evidence f cerebral vascular disease tended, in general, t have lwer median pnderal index values than did subjects withut cerebral vascular disease (fig. ). In ther wrds, relative bdy weight tended t be higher in subjects with cerebral vascular disease. These differences in median pnderal index values were mst prminent in males 4 t 49 years f age and females 5 t 59 and 6 t 69 years f age. Grups belw age 4 years were t small t be included in this cmparisn. A similar cmparisn f median pnderal index values fr grups f subjects with and withut ne r mre f cerebral vascular disease, athersclertic heart disease, diabetes mellitus, and hypertensin revealed an even mre striking relatinship between decreased pnderal index and the presence f ne r mre f these disease states (fig. 3). Thus, grups f 14 13 I 3 - a 1 14 - "5 13-1 - Q - 75 th percentile O --.^-- O "--c - _L 3 4 5 6 7 8 9 Females «. "» a D 5 th percentile 5 1 1 1 1 1 1 1 3 4 5 6 7 8 9 c FIGURE 1 percentile ^^ 75 lh percentile ^ ^ 3 5 ln percentile ^. 5 th percentile Pnderal index perceniile distributins fr given age grups. Strke, Vl. 5, May-June 1974 313
KLASSEN, LOEWENSON, RESCH <u - 14 Cerebral Vascular Disease Present Cerebral Vascular Disease Absent 14 13 Cses with CVO, ASHD, DM AND HYPERTENSION * A Cases with abve ABSENT > I 1 3 4 5 6 7 8 9 4 - Females 3 6 7 8 FIGURES Median pnderal index values (5th percentilesj fr subjects with and withut cerebral vascular disease. subjects with ne r mre f thse cnditins knwn t be assciated with increased cerebral athersclersis demnstrated the presence f increased relative bdy weight in all age grups ver 4. Grups f subjects with pnderal index values in the lwer and upper quartiles, respectively, were then cmpared by pltting median values f the cerebral athersclersis vessel scres btained frm these subjects (fig. 4). with lw pnderal index, that is, the relatively "verweight" grup, had mre severe cerebral athersclersis in all age grups frm the furth thrugh the eighth decades with median vessel scres being apprximately equal in subjects 8 years f age and lder. In females, a similar relatinship between "verweight" subjects and higher vessel scres culd nt be as readily identified, but the severity f cerebral athersclersis in this grup was apparently greater in the sixth and eighth decades. Because f the previusly demnstrated relatinship between increased cerebral athersclersis and the presence f cerebral vascular disease, athersclertic heart disease, diabetes mellitus and hypertensin, a similar cmparisn f vessel 1 1. 1 1 \ 3 4 5 6 7 FIGURE 3 1 1 8 9 Median pnderal index values (5th percentiles) fr subjects with and withut ne r mre f cerebral vascular disease fcvdj, athersclertic heart disease (ASHD), diabetes mellitus (DM) and hypertensin. scres between subjects in the lwer and upper quartiles f pnderal index distributin was made after exclusin f all subjects with these disease cnditins (fig. 5). When these exclusins were made, n clear relatinship between pnderal index and the severity f cerebral athersclersis culd be demnstrated. In ther wrds, it appeared that relative bdy weight by itself was nt retated t the degree r severity f athersclersis f cerebral arteries in this autpsy ppulatin. Irregularity f the curves resulting frm jining mid-decade median vessel scres as seen in figure 5 is prbably related t small sample sizes, especially in the ldest age grups. A cmparisn f the prevalence f cerebral vascular disease in grups f subjects in the lwer and upper pnderal index quartiles is made in table 3. These data suggest that cerebral vascular disease may have been present mre frequently in "verweight" males in the 4-year t 79-year age grups and in "verweight" females aged 5 t 69 and ver age 8. The remval f subjects with hypertensin, athersclertic heart disease and diabetes mellitus frm these grups left t few subjects t perfrm a similar cmparisn. Discussin The pnderal index is admittedly imperfect in its ability t accurately quantify degrees f "verweight" 314 Strke, Vl. 5, May-June 1974
BODY WEIGHT, CEREBRAL ATHEROSCLEROSIS AND CVD 4 A A Pnderal Index < 5 th percentile ("verweight") i Pnderl Index ^75 th percentile ("underweight") cs CO 3 *- Ap r,deral Index ^5* percentile ("verweight") Pnderl Index ^75 percentile ("underweight") 1 a - 1-6 7 FIGURE 4 Median vessel scres (5th percenlilesj fr subjects in the lwer ("verweight") and upper ("underweight") quarliles fpnderal index distributin. and "underweight" fr either individuals r grups. In the present study, hwever, the use f this index permitted identificatin f grups f subjects at bth extremes f relative weights at varying ages. The use f quartiles als bviated the need t establish ther criteria fr nrmal, "underweight" and "verweight." The use f terminal bdy weights in such a study als presents prblems in interpretatin inasmuch as sme patients may well have lst cnsiderable weight during their final illness. The mst likely effect f such weight lss wuld be that subjects wh were "verweight" befre their terminal illness were nt cnsidered "verweight" in this analysis. This wuld, in turn, tend t bscure sme f the differences in severity f cerebral athersclersis between grups f subjects in the "verweight" and "underweight" categries. Prir t the present study, there have been little pathlgical data available relating relative bdy weight with the degree f cerebral athersclersis r pathlgical and clinical evidence f cerebral vascular disease. 13 '" Life insurance studies and prspective studies such as the Framingham study 6 16> 16 ' have demnstrated increased frequency f hypertensin and crnary artery disease in "verweight" subjects. Other studies" have suggested that the apparent relatinship between besity and cardivascular dis- O CO 3 1 n 3 4 Females - - 5 6 s 1 *J 1 1 3 4 5 6 7 8 FIGURE 5 Median vessel scres (5th percentiles) fr subjects in the lwer and upper quartiles f pnderal index distributin excluding all subjects with ne r mre f cerebral vascular disease, athersclertic heart disease, diabetes mellitus and hypertensin. ease was due t an increased incidence f hypertensin and diabetes in the bese ppulatin. On the ther hand, a relatinship between besity and crnary artery disease may be present independent f the presence f hypertensin. 18 Prspective clinical studies f ischemic and hemrrhagic cerebral vascular disease have been incnclusive as t the rle f besity as a "risk factr" in the subsequent develpment f strke. 19 In the present study, grups f subjects with diseases r disrders assciated with increased cerebral athersclersis tended t have lwer median pnderal index values than did subjects withut these cnditins. This wuld tend t supprt the hypthesis that excessive bdy weight r besity may, indeed, be a "risk factr" fr the subsequent develpment f such cnditins. This cntentin als is supprted by the finding that the median cerebral athersclersis vessel scres tended t be higher in "verweight" subjects, especially in males. Furthermre, in many age grups, especially in males, clinical and/r pathlgical evidence f cerebral vascular disease appeared t be present mre frequently in the relatively "verweight" subjects. On the ther hand, when subjects with thse cnditins knwn t be assciated with increased ( / A t 8 Strke, Vl. 5, May-June 1974 3
KLASSIN, LOEWINSON, RESCH TABLE 3 Prevalence f Cerebral Vascular Disease in "Overweight" and "Underweight" Subjects Aaa greaa (year.) "Overweight"* Number with CVOJ MALI* % ilia "Underweight"! Number wltb CVDJ % 57 3.3 14.1.8 7.7 41.5 167-9 3-39 4-49 5-59 6-69 7-79 8 + Ttal 8 41 49 1 1 9 39 464 8 33 37 1 4.9 16.3 17.4 33. 4. 38.5 4.8 PIMALU 3 35 6 99 95 94 41 454 14 6 17 76 Aga grasp (yean) -9 3-39 4-49 5-59 6-69 7-79 8 + Ttal ilze 8 67 63 68 49 19 39 "Overweight"* Namber with CVDJ 4 7 11 59 % 6. 11.1 3.4 3.6 57.9 19.1 til* 17 8 56 64 71 51 19 36 "Underweight"! Numbar with CVDJ 3 3 11 18 8 43 * 5.3 A7.5 35.3 4.1 14.1 Pnderal index <, 5th percentile. fpnderal index > 75th percentile. = cerebral vascular disease. cerebral athersclersis were remved frm the grup cmparisns f median vessel scres, n cnsistent relatinships between bdy weight and severity f cerebral athersclersis culd be demnstrated. It is suggested, therefre, that excessive bdy weight r relative besity as measured by the pnderal index is nt, by itself, related t the severity f cerebral athersclersis. The data d nt preclude the pssibility that excessive bdy weight may be related t increased athergenesis in which, hwever, the cerebral arteries d nt participate t a degree detectable by the methds used in this study. It als is apparent that excessive bdy weight appears t be nly ne f a cmplex grup f factrs which may be related causally r casually t the develpment f athersclersis and vascular lesins f the nervus system. Thse additinal factrs which, in the presence f hypertensin and diabetes mellitus, appear t predispse sme individuals t the develpment f athersclersis and its cmplicatins still require further elucidatin. References 1. Sciety f Actuaries Build and Bld Pressure Study, 1959. Vl 1. Chicag, Sciety f Actuaries, 1959. Seltzer CG Sme re-evaluatins f the build and bld pressure itudy, 1959, as related t pnderal index, smatype and mrtality. New Eng J Med 74:54-59, 1966 3. Metrplitan Life Insurance Cmpany! Mrtality amng verweight men. Stat Bull Metrpl Life Ins C 41:6-1 (Feb) I96 4. Metrplitan Life Insurance Cmpany: Mrtality amng verweight wmen. Stat Bull Metrpl Life Ins C 41:1-4 (Mar) 196 5. Kannel WB, Brand N, Skinner JJ, et ah The relatin f adipsity t bld pressure and develpment f hypertensin. The Framingham study. Ann Int Med 67:48-59 (July) 1967 6. Chiang BN, Perlman LV, Epstein FHi Overweight and hypertensin: A review. Circulatin 39:43-41 (Mar) 1969 7. Chapman JM, Reeder LG, Brun ER, et al: Epidemilgy f vascular leiins affecting the central nervus system. The ccurrence f strkes in a (ample ppulatin under bservatin fr cardivascular disease. Amer J Public Health 36:191-1 (Feb) 1966 8. Paffenbarger RS, Williams JLi Chrnic disease in frmer cllege students. V. Early precursrs f fatal strke. Amer J Public Health 37:19-199 (Aug) 1967 9. Kannel WBi Current status f the epidemilgy f brain infarctin assciated with cclusive arterial disease. Strke :95-318 (July- Aug) 1971 1. Resch JA, Okabe N, Lewensn RB, et al: Pattern f vessel invlvement in cerebral athersclersis. J Atherscler Res 9i39-5, 1969 11. Lewensn RB, Berman JE, Resch J A: Reliability f measurements fr studies f cerebral athersclersis. Bimetrics 8:557-569 (June) 197 1. Klassen AC, Lewensn RB, Resch JAi Cerebral athersclersis in selected chrnic disease states. Athersclersis 18:31-336, 1973 316 Strke, Vl. 5, May-June 1974
BODY WEIGHT, CEREBRAL ATHEROSCLEROSIS AND CVD 13. Giertsen JC: Athersclersis in an autpsy series. 1. Relatin f nutritinal state t athersclersis. 11. General summary and cnclusin. Acta Pathl Micrbil Scand 67:35-31, 1967 14. Mntenegr MR, Slberg LA: Obesity, bdy weight, bdy length, and athersclersis. Lab Invest 18:594-63, 1968. Dawber TR, Mre FE, Mann GV: II. Crnary heart disease in the Framingham study. Amer J Public Health 47:4-4, 1957 16. Kagan A, Dawber TR, Kannel WB, et al: The Framingham study: A prspective study f crnary heart disease. Fed Prc 1 (Suppl 1 l):5-57, 196 17. Spain DM, Nathan DJ, Gellis M: Weight, bdy type and the prevalence f crnary athersclertic heart disease in males. Amer J Med Sci 45:97-1, 1963 18. Epstein FH, Ostrander LD, Jhnsn BC, et al: Epidemilgical studies f cardivascular disease in a ttal cmmunity Tecumseh, Michigan. Ann Int Med 6:117-1187, 1965 19. Kannel WB, Blaisdell FW, Giffrd R, et al: Risk factrs in strke due t cerebral infarctin. Strke :43-48 (Sept-Oct) 1971 Strke, Vl. 5, May-June 1974 317