The Prevalence of Coronary Artery Calcium Among Diabetic Individuals Without Known Coronary Artery Disease

Transcription

1 Joural of the America College of Cardiology Vol. 41, No. 6, by the America College of Cardiology Foudatio ISSN /03/$30.00 Published by Elsevier Sciece Ic. doi: /s (02) The Prevalece of Coroary Artery Calcium Amog Diabetic Idividuals Without Kow Coroary Artery Disease Diabetes ad Cardiovascular Disease Julie Ae Hoff, PHD, RN,* Lauretta Qui, PHD, RN, Alexader Sevrukov, MD,* Rebecca B. Lipto, PHD, MPH, BSN, Martha Daviglus, MD, PHD, Daiel B. Garside, MS, Niraj K. Ajmere, BS,* Sajay Gadhi, MD,* George T. Kodos, MD* Chicago, Illiois OBJECTIVES BACKGROUND METHODS RESULTS CONCLUSIONS We sought to examie the age ad geder distributio of coroary artery calcium (CAC) by diabetes status i a large cohort of asymptomatic idividuals. Amog idividuals with diabetes, coroary artery disease (CAD) is a major cause of morbidity ad mortality. Electro-beam tomography (EBT) quatifies CAC, a marker for atherosclerosis. Screeig for CAC by EBT was performed i 30,904 asymptomatic idividuals stratified by their self-reported diabetes status, geder, ad age. The distributio of CAC across the strata ad the associatio betwee diabetes ad CAC were examied. Compared with odiabetic idividuals ( 29,829), those with diabetes ( 1,075) had higher media CAC scores across all but two age groups (wome 40 to 44 years old ad me ad wome 70 years old). Overall, the likelihood of havig a CAC score i the highest age/geder quartile was 70% greater for diabetic idividuals tha for their odiabetic couterparts. Youger diabetic idividuals appear to have calcified plaque burde comparable to that of older idividuals without diabetes. These fidigs call for future research to determie if EBT-CAC screeig has a icremetal value over the curret CAD risk assesmet of idividuals with diabetes. (J Am Coll Cardiol 2003;41: ) 2003 by the America College of Cardiology Foudatio Approximately 10.3 millio Americas have physiciadiagosed diabetes, whereas a estimated 5.4 millio people are udiagosed (1). Cardiovascular complicatios are the major cause of diabetes-associated morbidity ad mortality, as two-thirds of people with diabetes die of heart or blood vessel disease (2 4). Routie assessmet of covetioal risk factors accouts for oly a portio of the icreased coroary artery disease (CAD) risk observed amog diabetic idividuals (5). Electro-beam tomography (EBT) is a oivasive tool for the detectio ad quatificatio of coroary artery calcium (CAC), a marker for atherosclerosis. The extet of CAC strogly correlates with the overall magitude of atherosclerotic plaque burde (6) ad with the developmet of subsequet coroary evets (7,8). Previously published reports have demostrated, i limited samples of diabetic idividuals, greater calcified plaque burde by EBT, as compared with odiabetic idividuals (9 12). The preset From the *Departmet of Medicie, Sectio of Cardiology, Uiversity of Illiois College of Medicie, Chicago; Departmet of Medical Surgical Nursig, Uiversity of Illiois College of Nursig, Chicago; Divisio of Pediatric Edocriology, Uiversity of Chicago, Chicago; ad Departmet of Prevetive Medicie, Northwester Uiversity School of Medicie, Chicago, Illiois. This research was supported with iteral fudig from the Uiversity of Illiois at Chicago, Departmet of Medicie, Sectio of Cardiology. Mauscript received Jue 6, 2002; revised mauscript received November 15, 2002, accepted November 27, study supplemets the existig reports of the associatio betwee EBT-CAC ad diabetes by examiig the age ad geder distributio of CAC i a large cohort of asymptomatic diabetic ad odiabetic idividuals. METHODS Study sample. Betwee 1993 ad 1999, 32,477 idividuals (30 to 90 years old) were self-referred for EBT CAC screeig. Before screeig, subjects completed a questioaire elicitig demographic ad CAD risk factor iformatio. Of these idividuals, 1,573 were excluded from this aalysis because of a history of cliical CAD. The Uiversity of Illiois at Chicago (UIC) Iteral Review Board approved the study protocol. Self-reported CAD risk factors icluded a history of smokig, diabetes, hypercholesterolemia, hypertesio, ad a family history of CAD. The defiitios of self-reported CAD risk factors have bee reported previously (13). The validity of self-reported histories of hypercholesterolemia, diabetes, ad hypertesio was examied i a peripheral study (14). The kappa coefficiets for hypercholesterolemia, diabetes, ad hypertesio were (p 0.001), (p 0.001), ad 0.36 (p 0.01), respectively. The icogruity observed for hypertesio was maily due to a abudace of idividuals previously diagosed with hypertesio whose high blood pressure was cotrolled with

2 JACC Vol. 41, No. 6, 2003 March 19, 2003: Hoff et al. Coroary Artery Calcium ad Diabetes 1009 Abbreviatios ad Acroyms ARIC atherosclerosis Risk i Commuities Study CAC coroary artery calcium CAD coroary artery disease EBT electro-beam tomography NHANES Natioal Health Ad Nutritio Educatio Survey UIC Uiversity of Illiois at Chicago life-style modificatio ad who preseted with ormal blood pressure at the time of examiatio. Electro-beam tomography. The EBT-CAC scas were obtaied usig a C-100 or C-150 scaer (GE Imatro, South Sa Fracisco, Califoria). Usig electrocardiographic triggerig at 60% to 80% of the ECG RR iterval, two sets of 100-ms/3-mm images (40 ad 20 slices) were acquired. The CAC score was calculated usig the Agatsto method (15). The details of the UIC scaig protocol have bee published elsewhere (13). Data aalysis. The study sample was stratified by geder ad ito eight exclusive five-year age groups (from 40 to 70 years old). Aalysis was coducted usig SPSS versio 10.0 for Widows (SPSS, Ic., Chicago, Illiois). The Ma-Whitey U test was used to compare media CAC scores betwee diabetic ad odiabetic idividuals by age group. Chi-square aalysis was used to compare the prevalece of risk factors ad CAC. Cotrollig for age ad body mass idex, a multivariable logistic regressio aalysis was used to examie the associatio betwee CAD risk factors ad CAC scores 75th percetile for age/geder (13). RESULTS Sample characteristics. The study sample cosisted of 22,188 me ad 8,716 wome (30 to 90 years old). Diabetes was reported by 747 of the me (3.4%) ad 328 of the wome (3.8%). Demographics, risk factors, ad CAC characteristics for the study sample stratified by geder ad diabetes status are summarized i Table 1. Geerally, diabetic idividuals were older ad had a greater prevalece of hypertesio, cigarette use, ad CAC, as compared with those without diabetes. Overall, the mea ( SD) total CAC score i the diabetic group was , as compared with i those without diabetes. The reported socioecoomic idicators (icome ad educatio) for both the diabetic ad odiabetic idividuals were higher tha the atioal averages. Despite the high socioecoomic status of the study sample, the uderrepresetatio of wome ad miorities, ad the use of self-referred idividuals, the prevalece figures for CAD risk factors i the preset study sample were similar to Table 1. Demographics, Risk Factors, ad CAC Characteristics of Me ad Wome With ad Without Diabetes Me Diabetes ( 747) No Diabetes ( 21,441) p Value Mea age (yrs) Aual icome $50, Educatio 12 years Family history of CAD Past or curret smokig Hypertesio Hypercholesterolemia Mea body mass idex (kg/m 2 ) Presece of CAC ( 0) Mea CAC score Media CAC score (iterquartile rage) 63 (5 365) 6 (1 80) Total CAC 75% age/geder percetile Wome Diabetes ( 328) No Diabetes ( 8,388) p Value Mea age (yrs) Aual icome $50, Educatio 12 years Family history of CAD Past or curret smokig Hypertesio Hypercholesterolemia Mea body mass idex (kg/m 2 ) Presece of CAC ( 0) Mea CAC score Media CAC score (iterquartile rage) 5 (0 104) 1 (0 11) Total CAC 75% age/geder percetile Differeces betwee diabetic ad odiabetic idividuals were examied usig the Pearso s chi-square test (for percetages), idepedet samples t test (for age, body mass idex, ad mea CAC score), ad Ma-Whitey U test (for media CAC score). Data are preseted as the mea value SD or percetage of subjects. CAC coroary artery calcium; CAD coroary artery disease.

3 1010 Hoff et al. JACC Vol. 41, No. 6, 2003 Coroary Artery Calcium ad Diabetes March 19, 2003: Table 2. Media CAC s of Me ad Wome With ad Without Diabetes Me Diabetes Media CAC No Diabetes Media CAC p Value Age group (years) , , , , , , Total , Wome Diabetes Media CAC No Diabetes Media CAC p Value Age group (years) , , , , Total , The Ma-Whitey U test was used to compare coroary artery calcium (CAC) scores betwee diabetic ad odiabetic subjects withi each five-year age group. The aalyses were performed separately for me ad wome. estimates for the geeral U.S. populatio, usig data from the Natioal Health Ad Nutritio Educatio Survey (NHANES) ad the Atherosclerosis Risk i Commuities (ARIC) study (16,17). Table 2 provides pairwise comparisos of media CAC scores by geder, age, ad diabetes status. Compared with odiabetic subjects, me ad wome with diabetes exhibited higher CAC scores across all ages, with the exceptio of wome 40 to 44 years of age ad me ad wome 70 years of age. Withi each five-year age group, diabetic me exhibited cosistetly higher CAC scores tha did diabetic wome (p for all comparisos), except for the yougest age group (subjects 40 years old; p 0.05). Table 3 provides the results of a logistic regressio aalysis examiig the associatio betwee CAD risk factors ad a total CAC score i the highest age/geder quartile. For both geders, every CAD risk factor was sigificatly associated with a total CAC score i the highest age/geder quartile. Diabetes was the strogest predictor for havig a CAC score i the highest quartile for both geders. Overall, the likelihood of havig a CAC score i the highest age/geder quartile was 70% greater for diabetic idividuals tha for their odiabetic couterparts. Amog me ad wome, a associatio betwee age ad the extet of CAC has bee demostrated previously (13). As diabetic idividuals were sigificatly older tha their odiabetic couterparts, the age-adjusted multivariable logistic regressio aalysis described previously was repeated Table 3. Associatio Betwee CAD Risk Factors ad the Highest Age ad Geder Quartile of Coroary Artery Calcium ( 75%) Amog Me ad Wome ( 30,904) Me Wome Odds Ratio p Value Odds Ratio p Value Age (yrs) ( ) ( ) 0.41 Body mass idex (kg/m 2 ) 1.04 ( ) ( ) Family history of CAD (yes/o) 1.19 ( ) ( ) 0.01 Hypercholesterolemia (yes/o) 1.23 ( ) ( ) Cigarette use (yes/o) 1.36 ( ) ( ) Hypertesio (yes/o) 1.41 ( ) ( ) Diabetes (yes/o) 1.73 ( ) ( ) The logistic regressio model was costructed usig block etry of all predictor variables. The aalyses were performed separately for me ad wome. CAD coroary artery disease.

4 JACC Vol. 41, No. 6, 2003 March 19, 2003: Hoff et al. Coroary Artery Calcium ad Diabetes 1011 usig a 3-to-1 age/geder frequecy-matched sample of 3,225 radomly selected odiabetic cotrol subjects. I this model, the associatios betwee CAD risk factors ad a total CAC score 75th percetile for age/geder were very similar to those reported for the umatched sample, with the exceptio of cigarette use ad hypercholesterolemia i me i whom the magitude of risk was similar but the sigificace at the 0.05 level was lost. DISCUSSION Electro-beam tomography is gaiig acceptace as a tool for the detectio of subcliical CAD ad for guidig diagostic ad treatmet strategies (18). This study reports the distributio of CAC i a large sample of diabetic me ad wome without kow CAD. Our fidigs demostrate that asymptomatic diabetic me ad wome have higher media CAC scores tha do their odiabetic couterparts, with a few exceptios. For wome 40 to 44 years of age ad me ad wome 70 years of age, the most probable explaatio for the lack of a differece i EBT- CAC media scores by diabetes status is a lack of power resultig from the small umber of idividuals i each group. It is also possible that the older diabetic idividuals i this study were log-term, well-cotrolled survivors or possibly ewly diagosed with diabetes. Aother fidig was that amog subjects with diabetes at ay give age, me exhibited sigificatly greater calcified plaque burde, as compared with wome. Amog the CAD risk factors examied, diabetes was the strogest correlate for a CAC score i the highest agespecific quartile for both geders, eve whe usig a age/geder-matched sample of odiabetic cotrol subjects. The use of EBT for the detectio of CAD i diabetic idividuals has bee studied previously. I a recet study, Schurgi et al. (9) examied the degree of CAC i a sample of 139 asymptomatic diabetic idividuals, as compared with the radomly selected odiabetic group. Amog diabetic subjects, 26% had scores 400, compared with 7.2% i the radomly selected odiabetic group. Aother group of researchers (Olso et al. [10]) foud that CAC had 84% sesitivity for cliical CAD i type I diabetic me ad 71% sesitivity i type I diabetic wome. Khaleeli et al. (11) determied that 168 symptomatic (agial) diabetic idividuals had a higher prevalece of CAC, as compared with 155 asymptomatic diabetic idividuals. Iterestigly, o sigificat differece was determied betwee diabetic me ad wome with regard to CAC scores at ay give age. The failure to show a sigificat differece, however, could be attributable to the small sample size ( 323) ad the small correlatio coefficiets (r 0.28 for me ad r 0.36 for wome) reported. There are some limitatios of the preset study, which will be addressed i future research. The CAD risk factors were assessed usig self-reportig, with o cliical measuremet. Yet, i a peripheral study, we foud high levels of agreemet betwee self-reported ad cliically measured diabetes status (14). I additio, all study subjects were self-referred, ad there is a cocer that self-referred idividuals may represet extremes of the populatio relative to health status. I cosiderig these limitatios, it is importat to ote that the prevalece rates for CAD risk factors i the study sample were comparable to those reported i two populatio-based studies (16,17). Also, oe-third of type II diabetes is udiagosed (19). It is quite possible that there were idividuals with impaired glucose tolerace or type II diabetes who were categorized as odiabetic. I light of this limitatio, the observed differeces by diabetes status would be atteuated, ad therefore it is possible that the differeces betwee diabetic ad odiabetic idividuals are greater tha we report. The cliical utility of oivasive evaluatio of atherosclerosis i asymptomatic diabetic idividuals remais uclear. Because diabetes places idividuals i the same risk category as idividuals with kow CAD (2), oivasive testig such as EBT-CAC screeig would do little to chage the curret cliical maagemet of traditioal cardiovascular risk factors. Yet future studies to determie whether CAC scores predict future cliical evets i asymptomatic idividuals with diabetes will help delieate a role for EBT i the cliical maagemet of diabetes (20). The icreasig use of imagig modalities i populatiobased studies ad cliical practice may ehace the utility of CAC screeig, which could be a importat tool i describig the atural history of coroary atherosclerosis i both impaired glucose tolerace ad diabetes. Amog prediabetic idividuals, especially those with the metabolic sydrome, CAC screeig could be particularly useful i the stratificatio of certai idividuals ito more aggressive risk factor maagemet regimes. I additio, EBT-CAC screeig results may potetially motivate idividuals i their CAD risk reductio efforts. Further studies are eeded to address these potetial uses of CAC screeig. Reprit requests ad correspodece: Dr. Julie Ae Hoff, DOM, Cardiology, 840 S. Wood Street (m/c 715), Chicago, Illiois jahoff@uic.edu. REFERENCES 1. Diabetes Statistics. Natioal Diabetes Iformatio Clearighouse. Bethesda, MD: Natioal Istitutes of Health, NIDDKD, NIH publicatio o , Grudy SM, Bejami IJ, Burke GL, et al. Diabetes ad cardiovascular disease: a statemet for healthcare professioals from the America Heart Associatio. Circulatio 1999;100: Geiss LS, Herma WH, Smith PJ, the Natioal Diabetes Data Group. Diabetes i America. Bethesda, MD: Natioal Istitutes of Health, NIDDKD, 1995: Hu FB, Stampfer MJ, Solomo CG, et al. The impact of diabetes mellitus o mortality from all causes ad coroary heart disease i wome: 20 years of follow-up. Arch Iter Med 2001;161: Hayde JM, Reave PD. Cardiovascular disease i diabetes mellitus type 2: a potetial role for ovel cardiovascular risk factors. Curr Opi Lipidol 2000;11:

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