Components of the Metabolic Syndrome and Risk of Cardiovascular Disease and Diabetes in Beaver Dam

Transcription

1 Epidemiology/Health Services/Psychosocial Research O R I G I N A L A R T I C L E Compoets of the Metabolic Sydrome ad Risk of Cardiovascular Disease ad Diabetes i Beaver Dam BARBARA E.K. KLEIN, MD RONALD KLEIN, MD KRISTINE E. LEE, MS OBJECTIVE To determie whether compoets of the metabolic sydrome precede the 5-year icidece of cardiovascular disease ad diabetes. RESEARCH DESIGN AND METHODS A populatio of idividuals aged years was evaluated from 1988 to 1990 ad agai 5 years later. Medical history, blood pressure, ad laboratory measures were obtaied at both examiatios followig the same protocols. Subjects without diabetes were classified accordig to level of glycemia, high blood pressure, high-risk lipid levels, high uric acid levels, ad proteiuria at baselie. History of icidet myocardial ifarctio, agia, stroke, ad diabetes was obtaied at follow-up. RESULTS Of the 4,423 subjects without diabetes, 6.9% had elevated levels of glycemia, 18.4% had high blood pressure, 82.7% had high-risk lipid levels (either high serum total cholesterol or low HDL cholesterol or high ratio of these two levels), 27% had elevated uric acid levels, 33.2% had high BMI, ad 3.3% had proteiuria ( 30 mg/dl). The risk of icidet cardiovascular disease 5 years later icreased with the umber of the compoets preset; 2.5% of those with oe compoet developed cardiovascular disease, whereas 14.9% of those with four or more compoets developed cardiovascular disease. Of those with oe compoet, diabetes developed i 1.1% 5 years later, whereas diabetes developed i 17.9% of those with four or more compoets. CONCLUSIONS Compoets of the metabolic sydrome are commo ad are associated with icidet cardiovascular disease ad diabetes after 5 years. Itervetios to alter BMI, lipid levels, ad blood pressure may decrease icidet diabetes ad cardiovascular disease. May persoal ad evirometal characteristics have bee foud to be associated with icreased risk of cardiovascular disease (CVD) (1 3). Although some of these characteristics may occur aloe (4), clusterig of risk factors is ot ucommo (5). The metabolic sydrome, defied by a cluster of risk factors icludig hypertesio, cetral obesity, ad dyslipidemia with or without hyperglycemia, seems to be associated Diabetes Care 25: , 2002 with icreased risk of macrovascular disease (5), which may exceed the sum of the risks icurred by each aloe, although this view is ot held uiversally (6 8). The features of the sydrome have bee reported to precede the detectio of overt diabetes (9) by as much as 10 years, at which time the kow icreased risk of CVD has bee documeted. Although other characteristics ad exposures icludig smokig (10), alcohol itake From the Departmet of Ophthalmology ad Visual Scieces, Uiversity of Wiscosi Medical School, Madiso, Wiscosi. Address correspodece ad reprit requests to Barbara E. K. Klei, MD, MPH, Departmet of Ophthalmology ad Visual Scieces, Uiversity of Wiscosi Madiso, 610 N. Walut Street, 460 WARF, Madiso, WI Received for publicatio 22 Jauary 2002 ad accepted i revised form 29 Jue Abbreviatios: CVD, cardiovascular disease; WHO, World Health Orgaizatio. A table elsewhere i this issue shows covetioal ad Système Iteratioal (SI) uits ad coversio factors for may substaces. (11), ad physical activity (12) may further modify risk, it is our purpose to determie whether by focusig o the compoets of this sydrome or closely related characteristics we will fid a icreased risk of CVD ad of overt diabetes ad whether a icrease i risk might be detected as soo as 5 years after assessig risk factor status. We evaluated this i a study iitially idetified to determie prevalece, icidece, ad risk factors for age-related eye disease. RESEARCH DESIGN AND METHODS A private cesus of the populatio of Beaver Dam, Wiscosi was performed from 1987 to 1988 (13). Idividuals aged years ( 4,926) were evaluated durig a 2.5-year period begiig March 1, Teets of the Declaratio of Helsiki were followed, istitutioal huma experimetatio committee approval was grated, ad each subject provided iformed coset. Durig the study visits, stadard measuremets ad questioaires were admiistered. All subjects idetified at the iitial cesus were ivited for the secod examiatio. Oly those participatig i the first ad secod examiatios ( 3,684; 2,092 wome ad 1,592 me) supplied iformatio pertiet to the curret article. The follow-up examiatios occurred 4.8 ( 0.4) years after the first evaluatios ad were performed i such a way that participats were see i approximately the same order as i the previous examiatios. Procedures at the follow-up were the same as at the baselie examiatios. Details have bee previously published (14 17). Blood pressure, height, ad weight were measured. Participats were asked whether a doctor had ever told them that they had agia, heart attack, stroke, diabetes, ad/or hypertesio. This selfreported history of agia, heart attack, or stroke was used to defie CVD at both visits. This was ot cofirmed by medical records. At the baselie examiatio, all subjects were asked to permit veipuc DIABETES CARE, VOLUME 25, NUMBER 10, OCTOBER 2002

2 Klei, Klei, ad Lee Table 1 Compoets of the metabolic sydrome at baselie Compoet Defiitio Mea SD % Elevatio glycemia 6.9 Glucose 140 mg/dl 4, Glycosylated Hemoglobi 7% 4, High blood pressure 18.4 Systolic 160 mmhg 4, Diastolic 90 mmhg 4, High-risk lipid levels 82.7 Serum total cholesterol 200 mg/dl 4, Serum HDL cholesterol 35 (me), 39 (wome) mg/dl 4, Lipid ratio (Total/HDL) 5.7 (me), 5.1 (wome) 4, BMI 30 kg/m 2 4, uric acid level 7.0 mg/dl 4, Proteiuria 30 mg/dl 4, ture to obtai serum for total cholesterol (18), HDL cholesterol (19), glycosylated hemoglobi (20), glucose (21), ad uric acid (22). These tests, except for serum uric acid, were repeated at the 5-year follow-up. Subjects were ot requested to fast. Proteiuria was defied as 30 mg/dl or more, as tested by a dipstick o a casual urie specime that was collected at the time of the study examiatio. Diabetes was defied as a previous history of diabetes (treated with isuli ad/or oral hypoglycemic agets ad/or diet) or hyperglycemia. Hyperglycemia here is defied as glycosylated hemoglobi 2 SDs above the mea for the appropriate age-sex group at the give examiatio or a casual blood glucose level 200 mg/dl (1.1 mmol/l). Newly diagosed diabetes was defied as o previous history of diabetes i the presece of glycosylated hemoglobi that was 2 SDs above the mea for the appropriate age-sex group. There were 50 such persos. A total of 446 persos had diabetes at the time of the baselie examiatio. We excluded data from these idividuals. Our defiitios of the compoets of the metabolic sydrome were adapted from Alberti ad Zimmet (7). The criteria they describe are impaired glucose itolerace, icludig frak diabetes or isuli resistace, ad two or more of a list icludig elevated arterial pressure, elevated plasma triglyceride ad/or low HDL cholesterol levels, cetral obesity or high BMI, ad microalbumiuria. They idicate that other compoets have bee described (e.g., hyperuricemia), but they do ot iclude these i their defiitio. The compoets we icluded were level of glycemia, hypertesio, serum total cholesterol level, serum HDL cholesterol level, ratio of serum total cholesterol to HDL cholesterol, serum uric acid level, obesity, ad proteiuria (Table 1). SAS statistical software was used to calculate 2 statistics, logistic regressio, ad Pearso correlatios. Tests of tred were calculated by the Matel-Haeszel method (23). RESULTS The baselie distributio of compoets of the metabolic sydrome that we have used to defie elevated risk are show i Table 1. serum total cholesterol ad elevatio of the ratio of total to HDL cholesterol (lipid ratio) derived from it are the most commo risk factors, followed by elevated BMI, uric acid level, ad blood pressure. For two of the lipid variables (serum HDL cholesterol ad ratio of total to HDL cholesterol), differet cutpoits are used to defie elevated values for wome ad me. glycosylated hemoglobi level, albumiuria, ad elevated blood glucose level were less commo. For the remaider of this study, we discuss oly elevated glycemia (either elevated serum glucose or elevated glycosylated hemoglobi), high-risk lipid levels (elevated total cholesterol, low HDL cholesterol, or elevated lipid ratio), ad high blood pressure risk factor (high systolic or high diastolic blood pressure). The pairwise relatioships of compoets of the metabolic sydrome withi subjects are show i Table 2. May are sigificatly associated with the others. Correlatio coefficiets for cotiuously measured variables, i geeral, reflected the fidigs from the dichotomous aalyses (correlatios ot show i Table 2). Strogest correlatios were betwee the lipid ratio ad BMI (0.25), lipid ratio ad uric acid level (0.34), BMI ad uric acid level (0.31), ad uric acid ad HDL cholesterol levels ( 0.30). The populatio was examied 5 years after the baselie examiatio, at which time iformatio about icidet myocardial ifarctio, stroke, ad agia durig that iterval was obtaied. The icideces were 3.0% for myocardial ifarctio, 1.5% for stroke, ad 4.0% for agia. These diagoses are cosidered collectively as CVD. Icideces of CVD for each compoet are show i Table 3. Because odds ratios were iflueced by age ad sex, the odds ratios are adjusted for these compoets. The greatest risks are associated with elevatios i level of glycemia ad presece of proteiuria. We computed the relative risk of developig CVD by the umber of these compoets at baselie (Table 4). The risk of icidet CVD is approximately six times greater whe four or more compoets are preset, compared with whe oe of the compoets are preset. Cotributios of the idividual compoets to clusters of factors associated with icreased risk of CVD are show i Table 5. For combiatios of risk factors (1, 2, etc.), elevated glycemia occurred i 1.0% of those with oe compoet, 6.1% of those with two compoets, 14.2% of those with three compoets, ad 40% of those with four or more compoets. High-risk lipid levels occurred most commoly i the combiatios of compo- DIABETES CARE, VOLUME 25, NUMBER 10, OCTOBER

3 Metabolic sydrome ad cardiovascular disease Table 2 Pairwise relatioships of compoets of the metabolic sydrome at baselie Compoet glycemia High blood pressure High-risk lipid levels BMI uric acid level Presece of proteiuria % P value % P value % P value % P value % P value % P value Glycemia Normal Blood pressure Normal High-risk lipid Abset levels Preset BMI Normal Uric acid level Normal Proteiuria No Yes ets that were associated with icreased risk of CVD. The relative risk of icidet diabetes by each compoet is show i Table 6. The measures of glycemia were most strogly related to icidet diabetes; elevated BMI, high blood pressure, ad elevated uric acid level also had sigificat relatioships. Idividuals with icreasig umbers of risk factors are at icreased risk of icidece of diabetes, such that those with four or more compoets are 35 times as likely to develop the disease as those with oe of the compoets at baselie (Table 7). CONCLUSIONS We have foud that compoets of the metabolic sydrome, as we defie them, i a populatio of idividuals without diagosed diabetes are relatively commo ad that they predict icidet CVD ad diabetes. The metabolic sydrome, origially described by Reave (5), has bee foud i may ethic groups (24). Isuli resistace may be the uderlyig pathophysiological basis of the sydrome. However, irrespective of uderstadig the specific metabolic relatioships, the cliical importace of determiig whether oe, two, or more of these frequetly measured compoets or variables closely related to them are most resposible for the lik to subsequet macrovascular disease lies i whether they ca be altered to reduce risk. Iterveig directly o glycemia i people who at the momet do ot carry a diagosis of diabetes is probably ot feasible. A more pragmatic approach might be to apply itervetios aimed at alterig levels of some of the other compoets of the metabolic sydrome (BMI, blood pressure, ad lipid levels) i a effort to forestall icidet heart disease ad diabetes. Treatig obesity, blood pressure, ad higher lipid levels is o easy matter either, but there likely would be beefits to may disease ed poits ot examied here ad to the quality of life if itervetios o these factors were successful. The recet Diabetes Prevetio Trial (25) attests to the efficacy of a itervetio to prevet diabetes based o alterig these risk factors. Our data suggest the possibility that decreasig eve oe or two of the compoets of the metabolic sydrome may reduce the overall risk of icidet CVD ad diabetes. The compoets of the sy- Table 3 Icidece of CVD by compoets of the metabolic sydrome Compoet Icidece Age- ad sex-adjusted odds ratio glycemia Normal 2, (1.40, 3.82) High blood pressure Normal 2, (0.77, 1.69) 0.50 High-risk lipid levels Normal , (1.21, 3.33) 0.01 BMI Normal 1, (0.88, 1.67) 0.24 uric acid level Normal 2, (1.19, 2.33) Proteiuria No 2, Yes (1.16, 5.12) 0.02 Table 4 Icidece of CVD by umber of compoets of the metabolic sydrome Compoets Icidece Odds ratio , (0.91, 4.16) (0.96, 4.40) (1.22, 5.98) (2.51, 13.66) DIABETES CARE, VOLUME 25, NUMBER 10, OCTOBER 2002

4 Klei, Klei, ad Lee Table 5 Cotributio of each compoet of the metabolic sydrome to umber of compoets i subjects at baselie examiatio ( 4,406) Compoets glycemia blood pressure drome are ot oly commo, but the correlatios amog them are, i may cases, sigificat. It may be that itervetio o oe of a pair of compoets may have a effect o the other. Therefore, decreasig BMI may have a beeficial effect o blood pressure, lipid levels, ad uric acid level. It is possible that iterveig o blood pressure may also have beeficial effects o the kidey, at least with respect to proteiuria. Although we ca, at best, oly High-risk lipid levels uric acid level BMI Proteiuria , , ifer the possibility of such beefits, they are plausible. We adapted, rather tha adopted, the World Health Orgaizatio (WHO) criteria described by Alberti ad Zimmet (7) for two reasos. The first is that our data were limited due to the study beig iitially desiged primarily as a study of agerelated eye disease. The secod is that we were iterested i the risks posed by the factors we examied i idividuals from a Table 6 Icidece of diabetes by compoets of the metabolic sydrome at baselie i Idividuals without diabetes Compoet Icidece Age- ad sex-adjusted odds ratio glycemia Normal 3, (12.15, 27.67) High blood pressure Normal 2, (1.07, 2.55) 0.02 High-risk lipid levels Normal , (0.88, 2.74) 0.13 BMI Normal 2, , (2.54, 5.55) uric acid level Normal 2, (1.36, 3.01) Proteiuria No 3, Yes (0.30, 3.19) 0.98 Table 7 Icidece of diabetes by umber of compoets of the metabolic sydrome Compoets Icidece Odds ratio , (0.39, 7.72) (1.44, 24.98) (2.22, 39.59) (7.93, ) geeral populatio who did ot have overt diabetes. Although our study desig is ot ideal for evaluatig the impact of a strictly defied study of the predictive ability of the WHO (or Natioal Cholesterol Educatio Program) (26) criteria, we believe that our fidigs complemet such studies. We ote several limitatios to our ivestigatio. Participats at the secod examiatio were youger, had slightly lower serum cholesterol levels, had lower total HDL cholesterol ratios, had lower serum uric acid levels, were less likely to have CVD, ad were less likely to have hypertesio tha those who participated oly i the baselie exam. Our diagoses of CVD are by selfreport. This may lead to over- or uderreportig. Mortality from CVD is ot icluded, because at this time, we do ot have these data. This likely results i a uderestimate of cardiovascular evets because of those who gave o history of the coditio but died of it. At this time, we caot estimate the effect of this o icidece of CVD, or ca we determie its effects o the risk factor aalyses. Lastly, our populatio is middle-aged, predomiatly white, ad rural. Therefore, we caot make ifereces beyod a similar group. These limitatios otwithstadig, we have foud that compoets of the metabolic sydrome sigly, ad i combiatio, are commo ad precede icidet CVD ad diabetes. This is despite the fact that the levels of the compoets we defied as high risk were ot very high. I additio, icreased risk ca be observed as soo as 5 years later. This heightes the importace of determiig ways to itervee o some or all of the compoets ad implemetig such itervetios promptly. Ackowledgmets This work was supported by Natioal Istitutes of Health Grat EY06594 (to R.K. ad B.E.K.K.). Refereces 1. Truett J, Corfield J, Kael W: A multivariate aalysis of the risk of coroary heart disease i Framigham. J Chro Dis 20: , Saito I, Folsom AR, Bracata FL, Duca BB, Chambless LE, McGover PG: Notraditioal risk factors for coroary DIABETES CARE, VOLUME 25, NUMBER 10, OCTOBER

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